WO2024218751A1

WO2024218751A1 - Oil free lipid nanoparticles for stabilizing hydrophobic agents and methods of use thereof

Info

Publication number: WO2024218751A1
Application number: PCT/IB2024/053865
Authority: WO
Inventors: Adam Garland; Brian SLOAT
Original assignee: Disruption Labs Inc
Current assignee: Disruption Labs Inc
Priority date: 2023-04-21
Filing date: 2024-04-19
Publication date: 2024-10-24
Anticipated expiration: 2025-10-21
Also published as: AU2024259184A1

Abstract

Some embodiments pertain to compositions comprising lipid nanoparticles comprising an active agent, a phospholipid, and a plant extract. Said compositions can be dried or aqueous, and can be utilized in compositions for associated methods of delivery of therapeutic ingredients to subjects. In several embodiments, the compositions are stable for prolonged periods of time and provide enhanced bioavailability.

Description

OIL FREE LIPID NANOPARTICLES FOR STABILIZING HYDROPHOBIC AGENTS AND METHODS OF USE THEREOF

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63/461,088, filed April 21, 2023, U.S. Provisional Patent Application No. 63/599,714, filed November 16, 2023, and U.S. Provisional Patent Application No. 63/599726, filed November 16, 2023, each of which are incorporated by reference in their entirety.

BACKGROUND

I. Field of the Disclosure

[0002] This disclosure relates to at least the fields of nanoparticles, drug delivery, nutraceuticals, consumer products, and medicine.

[0003] This disclosure relates generally to lipid nanoparticle compositions (e.g., liposomal, oil-in-water emulsions, etc.), compositions comprising the same, and their use in methods for the delivery of active ingredients.

II. Description of the Related Art

[0004] Currently, several plant extracts, fungal extracts, and/or vitamins are used as nutraceuticals. A nutraceutical, also called a bioceutical, is a pharmaceutical alternative which may have physiological benefits. Currently in the U.S.A., nutraceuticals are largely unregulated, as they exist in the same category as dietary supplements and food additives by the Food and Drug Administration (FDA), under the authority of the Federal Food, Drug, and Cosmetic Act.

[0005] The delivery of nutraceuticals is recognized to have great potential to treat a variety of diseases and conditions. Thus, the area of supplementation with nutraceuticals has seen a dramatic increase in the last few years. However, this increase in interest has led to many manufacturers rushing products to market that may be unsafe and/or that produce highly variable outcomes. For example, current delivery systems for active ingredients (e.g., vitamins, nutrients, plant/fungal extracts, etc.) vary widely, making their effects unpredictable. Thus, the active ingredients may have widely variable bioavailability and/or stability.

[0006] Current delivery systems for active ingredients can also suffer from a variety of problems. For example, with several current methodologies and compositions, distribution of nanoparticles within a composition and/or the active ingredients within nanoparticles may suffer from instability. This instability can result in low short term and/or long-term shelf stability of nanoparticle compositions and/or compositions comprising the same. Furthermore, current nanoparticle formulations may distribute unevenly through a solution or a liquid medium, which may lead to uneven distribution of active ingredients. Uneven distribution may result in nanoparticles forming a solid layer, precipitating out of a solution, and/or associated active ingredients having reduced bioavailability when delivered to a subject. In addition, some nanoparticles rely on the use of synthetic compounds for stability, which can make the nanoparticles unsuitable or undesirable for topical and/or internal use on humans.

BRIEF SUMMARY

[0007] Applicant has found that compositions as described herein can provide stable nanoparticles capable of carrying a broad range of compounds of interest, such as active agents, hydrophobic compounds, hydrophilic compounds, plant extracts, etc. In some instances, the nanoparticles are made of only natural materials (e.g., do not contain compounds that are not found in nature). In some instances, the nanoparticles may stay stable over months of storage, may stay in suspension over months of storage, and/or may reduce degradation of the compounds of interest as compared to the compounds of interest not in a nanoparticle or in a different nanoparticle. In some instances, the nanoparticles may be in two or more different forms of nanoparticles (e.g., liposome, micelle, nanoemulsion, multi-lamellar, double liposome, solid lipid particles). In some instances, the nanoparticles are simpler to produce, such as requiring no or less microfluidization or high-pressure homogenization. In some instances, the concentration of the compound of interest may be higher than that which is achievable with other nanoparticle formulations or in an aqueous solution without a nanoparticle.

[0008] Certain aspects of the disclosure comprise a composition comprising a plurality of lipid nanoparticles comprising: 5 to 60 wt. % of at least one phosphatidylcholine; 0 to 40 wt. % of a bulking agent; 0.01 to 20 wt. % of an active agent; and 0.1 to 20 wt. % of at least one plant extract. In some instances, the composition comprises 5 to 30 wt. % of a phosphatidylcholine; 0 to 20 wt. % of a bulking agent; 0.1 to 10 wt. % of an active agent; 0.5 to 10 wt. % of at least one plant extract; and 25.0 to 93.9 wt. % of water. In some instances, the composition does or does not include a bulking agent. In some instances, the composition comprises about 3.0 wt. % to about 9.0 wt. % of the bulking agent. In some instances, the bulking agent comprises a carbohydrate, polymer, maltodextrin, and/or mannitol. In some instances, the at least one plant extract comprises an extract of Tribulus terrestris, Yucca schidigera, Quillaja saponaria, Camellia sinesis, and/or Glycyrrhiza glabra. In specific instances, the at least one plant extract comprises a de-oiled plant extract.

[0009] In some instances, the composition further comprises 1-Lysophosphatidylcholine (1-LPC), 2-Lysophosphatidylcholine (2-LPC), Phosphatidylethanolamine (PE), N- acylphosphatidylethanolamine (APE), Phosphatidylinositol (PI), and/or Phosphatidic acid (PA). In some instances, the concentration of PI and/or PE is significantly greater than the concentration of 1-LPC, 2-LPC, APE, and/or PA. In some instances, the concentration of 1- LPC, 2-LPC, PE, APE, PI, and/or PA are at or below l/10^th the concentration of phosphatidylcholine. In some instances, the composition comprises about 0 wt. % to about 5.0 wt. % and/or about 0 wt. % to about 0.5 wt. % of an antioxidant. In some instances, greater than about 80% of the active agent is comprised in a lipid nanoparticle.

[0010] In some instances, the composition further comprises at least one or more buffers, one or more solvents, and/or one or more preservatives. In specific instances, the one or more buffers comprises sodium bicarbonate and/or sodium carbonate, the one or more solvents comprises ethanol, and the one or more preservatives comprises citric acid monohydrate, potassium sorbate, sodium benzoate, and/or a natural preservative. In some instances, the composition comprises sodium bicarbonate at about 0.0015 wt % to about 0.06 wt.% and/or sodium carbonate at about 0.0015 wt % to about 0.06 wt. %; and citric acid monohydrate at about 0.003 wt. % to about 0.4 wt. %, potassium sorbate at about 0.003 wt. % to about 0.4 wt. %, sodium benzoate at about 0.003 wt. to about 0.4 wt %, and/or natural preservative at about 0.003 wt. % to about 2.0 wt. %. In some instances, the natural preservative comprises a mushroom extract. In some instances, the mushroom extract is from a stem of a white button mushroom. In some embodiments, the mushroom extract is comprised in CHIB ER™.

[0011] In some instances, the active agent comprises a hydrophilic active agent or a hydrophobic active agent. In some instances, the active agent has a greater wt. % solubility in either water or ethanol than in medium chain triglycerides. In some instances, the active agent comprises a polyphenol and/or a flavonoid. In specific instances, the flavonoid is a prenylated flavonoid. In specific instances, the prenylated flavonoid is xanthohumol. In some embodiments, the flavonoid xanthohumol is comprised in XANTHOFLAV™ and/or XANTHOFLAV™ PURE. In some embodiments, the flavonoid xanthohumol is comprised in XANOHOP™ and/or XANOHOP™ GOLD. In some instances, the active agent comprises xanthohumol and additional hop prenylated flavonoids. In some instances, at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of about 60%, for at least 1 month. In some instances, at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 4 months. In some instances, at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 8 months.

[0012] In some instances, the weight ratio of the phosphatidylcholine to the active agent is about 12: 1 to about 3 :2, or about 11 : 1 to about 5 : 1. In some instances, the phosphatidylcholine is from a sunflower. In some instances, the phosphatidylcholine comprises a compound with a structure of:

In some instances, the composition comprises: 5 to 25 wt. % of the phosphatidylcholine; 0.1 to 10 wt. % of the active agent; 0 to 7.5 wt. % of the bulking agent; 2.5 to wt. 10 % of at least one plant extract; and 25 to 89.9 wt. % water. In some instances, the composition comprises: 10 to 25 wt. % the phosphatidylcholine; 1 to about 2.5 wt. % of the active agent; 0 to 5 wt. % the bulking agent; 5 to wt. 10 % of at least one plant extract; and 50 to about 70 wt. % water.

[0013] In some instances, the composition consists essentially of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and optionally the water. In some instances, the composition consists of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and the water. In some instances, the composition further comprises about 0 wt. % to about 0.5 wt. % of an antioxidant. In some instances, the composition comprises 0.01 to 5.0 wt. % or 0.1 to 1.0 wt. % of ethanol. In some instances, the composition further comprises the bulking agent comprises a maltodextrin based bulking agent. In some instances, the composition further comprises the bulking agent comprises a mannitol based bulking agent. In some instances, the plurality of lipid nanoparticles has an average density of about 0.90 g/cm³ to about 1.30 g/cm³. In some instances, the plurality of lipid nanoparticles has an average density of about 0.993 g/cm³ to about 1.10 g/cm³. In some instances, the lipid nanoparticles comprise liposomes and/or emulsion particles. In some instances, at least about 90 % of the plurality of lipid nanoparticles are liposomes. In some instances, the plurality of lipid nanoparticles has an average size ranging from about 30 nanometers (nm) to about 200 nm, about 50 nm to about 150 nm, and/or about 100 nm to about 150 nm. In some instances, 25% to 100%, 50% to 100%, 75% to 100%, and/or 95% to 100% of the lipid nanoparticles are liposomes.

[0014] In some instances, the active agent is comprised within either an inner surface of the nanoparticle, within an outer surface of the nanoparticle, and/or within a lipid bilayer of the nanoparticle. In specific instances, the active agent is comprised within the lipid bilayer of the nanoparticle. In some instances, the majority of nanoparticles are unilamellar. In some instances, the composition comprising multilamellar nanoparticles. In some instances, less than about 20% or less than about 10% of the lipid nanoparticles are emulsion particles.

[0015] In some instances, the composition has a turbidity of about 0 to about 5000 Nephelometric Turbidity Units (NTU) at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the composition has a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the composition has a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the composition has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the composition has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for about 1 month at a relative humidity of about 75%.

[0016] In some instances, the composition does not include a sterol and/or a triglyceride. In some instances, the composition is free of synthetic surfactants and is free of synthetic emulsifiers at concentrations greater than about 1/10^th that of phosphatidylcholine. In some instances, the composition comprises less than about 2.5 wt. % of emulsifiers other than phosphatidylcholine. In some instances, the composition is configured such that, upon storage for a period of one month at room temperature, the average size of the nanoparticles changes by less than about 20%. In some instances, the polydispersity index (PDI) of the plurality of lipid nanoparticles in the composition is about 0.01 to about 0.8, about 0.05 to about 0.5, and/or about 0.1 to about 0.5.

[0017] Certain aspects of the disclosure comprise an aqueous formulation comprising the composition described herein. In some instances, the composition is comprised in a second composition, and does not settle or separate from the second composition when stored for at least one month at a temperature of about 4 °C to about 20 °C. In some instances, the aqueous formulation comprises 50 wt. % to about 95.0 wt. %, 60.0 wt. % to about 80.0 wt. %, 8.0 wt. % to about 30.0 wt. %, and/or 17.0 wt. % to about 21.0 wt. % of the lipid nanoparticles.

[0018] In some instances, the aqueous formulation has a turbidity of about 0 to about 5000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the aqueous formulation has a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the aqueous formulation has a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%. In some instances, the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for 1 month at a relative humidity of about 75%.

[0019] In some instances, the aqueous formulation does not settle or separate when stored for at least one month at a temperature of about 20 °C. In some instances, the aqueous formulation is configured such that, upon storage for a period of one month at room temperature, the average size of the plurality of nanoparticles changes by less than about 20%. In some instances, polydispersity index (PDI) of the plurality of nanoparticles in the aqueous formulation is about 0.01 to about 0.8, about 0.05 to about 0.5, about 0.10 to about 0.5. In some instances, the aqueous formulation maintains a turbidity (EBC) of less than about 20 EBC, less than about 15 EBC, less than about 10 EBC, less than about 7 EBC, less than about 4 EBC, less than about 2.5 EBC, and/or less than about 1 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles. In some instances, the aqueous formulation maintains a turbidity (EBC) of less than about 300%, less than about 250%, less than about 200%, less than about 150%, less than about 125%, less than about 115% and/or less than about 110% of the turbidity of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles. In some instances, the aqueous formulation maintains a turbidity (EBC) that does not significantly differ from the turbidity (EBC) of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[0020] Certain aspects of the disclosure comprise an ingestible composition comprising the composition described herein. In some instances, the ingestible composition is a beverage, comprising at least about 50.0 wt. % water. In specific instances, the ingestible composition is a fermented beverage, a carbonated beverage and/or a beer. In some instances, the composition or aqueous composition reduces the formation of acetyl aldehyde or beta-damascenone in the beer. In some instances, the composition does or does not include alcohol. In some instances, the composition comprises about 0.01 wt. % to about 10.0 wt % alcohol, about 2.0 wt % to about 9.0 wt. % alcohol, and/or about 3.0 wt. % to about 8.0 wt. % alcohol.

[0021] In some instances, the composition comprises an aqueous formulation and the plurality of the nanoparticles. In some instances, the ingestible composition comprises about 10 to about 20 milligrams of the plurality of nanoparticles per about 1 gram of the ingestible composition. In some instances, the turbidity of the composition is not perceivable to the unaided eye. In some instances, the turbidity of the ingestible composition is within about 20% of the turbidity of a control ingestible composition that is the same as the ingestible composition except without the plurality of nanoparticles. In some instances, the turbidity of the composition does not increase by more than about 20%, when stored for 5 days at greater than 38 °C, or the turbidity of the composition increases less than about 15%, when stored for at least 5 days at greater than about 38 °C. In some instances, the pH of the composition is about 2.5 to 9.5, about 5.5 to about 7.5, about 6.0 to about 7.0, and/or about 6.3 to about 6.7.

[0022] In some instances, the composition has a negligible impact on the rate of foam decay of a carbonated beverage in which it is present. In some instances, the rate of foam decay in a carbonated beverage in which the composition is present is no greater than 150% of the rate of foam decay rate in the same carbonated beverage without the presence of the composition under similar conditions. In some instances, the rate of foam decay in a carbonated beverage in which the composition is present is no greater than 100% of the rate of foam decay rate in the same carbonated beverage without the presence ofthe composition under similar conditions. In some instances, the rate of foal decay in a carbonated beverage in which the composition is present is no greater than 150, 145, 140, 135, 130, 125, 120, 115, 110, 105, or 100% ofthe rate of foam decay rate in the same carbonated beverage without the presence of the composition under similar conditions.

[0023] Certain aspects of the disclosure comprise a method of making the ingestible composition described herein, the method comprising combining the composition described herein with an ingestible item. In some instances, the ingestible item is a beverage. In specific instances, the beverage is a beer. In some instances, the ingestible composition comprises about 10 to about 20 milligrams of the plurality of nanoparticles per about 1 gram of the ingestible item.

[0024] Certain aspects of the disclosure comprise a method of ingesting the ingestible composition described herein by a subject, the method comprising ingesting the ingestible composition. In some instances, ingesting the ingestible composition prevents or treats cancer in the subject. In some instances, ingesting the ingestible composition prevents or treats inflammation in the subject. In some instances, ingesting the ingestible composition reduces low-density lipoprotein levels and/or increases high-density lipoprotein levels in the subject. In some instances, ingesting the ingestible composition aids in recovery from a SARS-CoV-2 infection in the subject.

[0025] Certain aspects of the disclosure comprise a method of preserving a perishable composition, the method comprising combining the composition described herein to the perishable composition, wherein the composition preserves the perishable composition. In some instances, the perishable composition is an ingestible composition. In some instances, the perishable composition is a topical skin composition.

[0026] Certain aspects of the disclosure comprise atopical skin care composition. In some instances, the topical skin care composition is an emulsion. In specific instances, the emulsion is an oil-in-water emulsion. In some instances, the topical skin care composition comprises at least about 50.0 wt. % water. In some instances, the plurality of nanoparticles is comprised within an aqueous phase of the topical skin care composition.

[0027] Certain aspects of the disclosure comprise a method of applying the topical skin care composition to skin, the method comprising applying the topical skin care composition to the skin. In some instances, the method further comprises treating a skin condition. In some instances, the skin condition is a fine line, a wrinkle, uneven skin tone, hyperpigmented skin, or inflamed skin. In some instances, the topical skin care composition reduces skin inflammation. [0028] Aspect 1 is directed to a composition comprising a plurality of lipid nanoparticles comprising: 5 to 60 wt. % of at least one phosphatidylcholine; 0 to 40 wt. % of a bulking agent; 0.01 to 20 wt. % of an active agent; and 0. 1 to 20 wt. % of at least one plant extract.

[0029] Aspect 2 is directed to the composition of Aspect 1, comprising: 5 to 30 wt. % of a phosphatidylcholine; 0 to 20 wt. % of a bulking agent; 0.1 to 10 wt. % of an active agent; 0.5 to 10 wt. % of at least one plant extract; and 25.0 to 93.9 wt. % of water.

[0030] Aspect 3 is directed to the composition of Aspects 1 or 2, wherein the composition does not include a bulking agent.

[0031] Aspect 4 is directed to the composition of Aspects 1 or 2, wherein the composition comprises a bulking agent.

[0032] Aspect 5 is directed to the composition of Aspect 4, wherein the composition comprises about 3.0 wt. % to about 9.0 wt. % of the bulking agent.

[0033] Aspect 6 is directed to the composition of Aspects 4 or 5, wherein the bulking agent comprises a carbohydrate and/or polymer.

[0034] Aspect 7 is directed to the composition of Aspect 6, wherein the bulking agent comprises maltodextrin and/or mannitol.

[0035] Aspect 8 is directed to the composition of Aspects 1 to 7, wherein the at least one plant extract comprises an extract of Tribulus terrestris, Yucca schidigera, Quillaja saponaria, Camellia sinesis, and/or Glycyrrhiza glabra.

[0036] Aspect 9 is directed to the composition of Aspects 1 to 8, wherein the at least one plant extract comprises a de-oiled plant extract.

[0037] Aspect 10 is directed to the composition of Aspects 1 to 9, further comprising 1- Lysophosphatidylcholine (1-LPC), 2-Lysophosphatidylcholine (2-LPC), Phosphatidylethanolamine (PE), N-acylphosphatidylethanolamine (APE), Phosphatidylinositol (PI), and/or Phosphatidic acid (PA).

[0038] Aspect 11 is directed to the composition of Aspect 10, wherein the concentration of PI and/or PE is significantly greater than the concentration of 1-LPC, 2-LPC, APE, and/or PA. [0039] Aspect 12 is directed to the composition of Aspects 10, wherein the concentration of 1-LPC, 2-LPC, PE, APE, PI, and/or PA are at or below l/10^th the concentration of phosphatidylcholine .

[0040] Aspect 13 is directed to the composition of Aspects 1 to 12, comprising: about 0 wt. % to about 5.0 wt. % of an antioxidant.

[0041] Aspect 14 is directed to the composition of Aspects 1 to 13, comprising: about 0 wt. % to about 0.5 wt. % of an antioxidant. [0042] Aspect 15 is directed to the composition of Aspects 1 to 14, wherein greater than about 80% of the active agent is comprised in a lipid nanoparticle.

[0043] Aspect 16 is directed to the composition of Aspects 1 to 15, wherein the composition further comprises at least one or more buffers, one or more solvents, and/or one or more preservatives.

[0044] Aspect 17 is directed to the composition of Aspect 16, wherein the one or more buffers comprises sodium bicarbonate and/or sodium carbonate, the one or more solvents comprises ethanol, and the one or more preservatives comprises citric acid monohydrate, potassium sorbate, sodium benzoate, and/or a natural preservative.

[0045] Aspect 18 is directed to the composition of Aspect 17, comprising: sodium bicarbonate at about 0.0015 wt % to about 0.06 wt.% and/or sodium carbonate at about 0.0015 wt % to about 0.06 wt. %; and citric acid monohydrate at about 0.003 wt. % to about 0.4 wt. %, potassium sorbate at about 0.003 wt. % to about 0.4 wt. %, sodium benzoate at about 0.003 wt. to about 0.4 wt %, and/or natural preservative at about 0.003 wt. % to about 2.0 wt. %.

[0046] Aspect 19 is directed to the composition of Aspects 17 to 18, wherein the natural preservative comprises a mushroom extract.

[0047] Aspect 20 is directed to the composition of Aspect 19, wherein the mushroom extract is from a stem of a white button mushroom.

[0048] Aspect 21 is directed to the composition of Aspects 1 to 20, wherein the active agent comprises a hydrophilic active agent.

[0049] Aspect 22 is directed to the composition of Aspects 1 to 20, wherein the active agent comprises a hydrophobic active agent.

[0050] Aspect 23 is directed to the composition of Aspects 1 to 22, wherein the active agent has a greater wt. % solubility in either water or ethanol than in medium chain triglycerides.

[0051] Aspect 24 is directed to the composition of Aspects 1 to 23, wherein the active agent comprises a polyphenol.

[0052] Aspect 25 is directed to the composition of Aspects 1 to 24, wherein the active agent comprises a flavonoid.

[0053] Aspect 26 is directed to the composition of Aspect 25, wherein the flavonoid is a prenylated flavonoid.

[0054] Aspect 27 is directed to the composition of Aspect 26, wherein the prenylated flavonoid is xanthohumol.

[0055] Aspect 28 is directed to the composition of Aspects 1 to 27, wherein the active agent comprises xanthohumol and additional hop prenylated flavonoids. [0056] Aspect 29 is directed to the composition of Aspects 27 to 28, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of about 60%, for at least 1 month.

[0057] Aspect 30 is directed to the composition of Aspect 29, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 4 months.

[0058] Aspect 31 is directed to the composition of Aspect 29, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 8 months.

[0059] Aspect 32 is directed to the composition of Aspects 1 to 31, wherein the weight ratio of the phosphatidylcholine to the active agent is about 12: 1 to about 3:2.

[0060] Aspect 33 is directed to the composition of Aspect 32, wherein the weight ratio of the phosphatidylcholine to the active agent is about 11 : 1 to about 5: 1.

[0061] Aspect 34 is directed to the composition of Aspects 1 to 33, wherein the phosphatidylcholine is from a sunflower.

[0062] Aspect 35 is directed to the composition of Aspect 34, wherein the phosphatidylcholine comprises a compound with a structure of:

[0063] Aspect 36 is directed to the composition of Aspects 1 to 35, comprising: 5 to 25 wt. % of the phosphatidylcholine; 0.1 to 10 wt. % of the active agent; 0 to 7.5 wt. % of the bulking agent; 2.5 to wt. 10 % of at least one plant extract; and 25 to 89.9 wt. % water.

[0064] Aspect 37 is directed to the composition of Aspects 1 to 36, comprising: 10 to 25 wt. % the phosphatidylcholine; 1 to about 2.5 wt. % of the active agent; 0 to 5 wt. % the bulking agent; 5 to wt. 10 % of at least one plant extract; and 50 to about 70 wt. % water.

[0065] Aspect 38 is directed to the composition of Aspects 1 to 37, consisting essentially of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and optionally the water. [0066] Aspect 39 is directed to the composition of Aspects 36 or 37, consisting of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and the water.

[0067] Aspect 40 is directed to the composition of Aspects 1 to 39, further comprising: about 0 wt. % to about 0.5 wt. % of an antioxidant.

[0068] Aspect 41 is directed to the composition of Aspects 1 to 40, wherein the composition comprises 0.01 to 5.0 wt. % of ethanol.

[0069] Aspect 42 is directed to the composition of Aspects 1 to 41, wherein the composition comprises 0.1 to 1.0 wt. % of ethanol.

[0070] Aspect 43 is directed to the composition of Aspects 1 to 42, wherein the bulking agent comprises a maltodextrin based bulking agent.

[0071] Aspect 44 is directed to the composition of Aspects 1 to 43, wherein the bulking agent comprises a mannitol based bulking agent.

[0072] Aspect 45 is directed to the composition of Aspects 1 to 44, wherein the plurality of lipid nanoparticles has an average density of about 0.993 g/cm³ to about 1.02 g/cm³.

[0073] Aspect 46 is directed to the composition of Aspects 1 to 45, wherein the lipid nanoparticles comprise liposomes and/or emulsion particles.

[0074] Aspect 47 is directed to the composition of Aspect 46, wherein at least about 90 % of the plurality of lipid nanoparticles are liposomes.

[0075] Aspect 48 is directed to the composition of Aspects 1 to 47, wherein the plurality of lipid nanoparticles has an average size ranging from about 30 nanometers (nm) to about 200 nm.

[0076] Aspect 49 is directed to the composition of Aspects 1 to 48, wherein the plurality of lipid nanoparticles has an average size ranging from about 50 nm to about 150 nm.

[0077] Aspect 50 is directed to the composition of Aspects 1 to 49, wherein the plurality of lipid nanoparticles has an average size ranging from about 100 nm to about 150 nm.

[0078] Aspect 51 is directed to the composition of Aspects 1 to 50, wherein 25% to 100% of the lipid nanoparticles are liposomes.

[0079] Aspect 52 is directed to the composition of Aspects 1 to 51, wherein 50% to 100% of the lipid nanoparticles are liposomes.

[0080] Aspect 53 is directed to the composition of Aspects 1 to 52, wherein 75% to 100% of the lipid nanoparticles are liposomes.

[0081] Aspect 54 is directed to the composition of Aspects 1 to 53, wherein 95% to 100% of the lipid nanoparticles are liposomes. [0082] Aspect 55 is directed to the composition of Aspects 1 to 54, wherein the active agent is comprised within either an inner surface of the nanoparticle, within an outer surface of the nanoparticle, and/or within a lipid bilayer of the nanoparticle.

[0083] Aspect 56 is directed to the composition of Aspect 55, wherein the active agent is comprised within the lipid bilayer of the nanoparticle.

[0084] Aspect 57 is directed to the composition of Aspects 1 to 56, wherein the majority of nanoparticles are unilamellar.

[0085] Aspect 58 is directed to the composition of Aspects 1 to 57, comprising multilamellar nanoparticles.

[0086] Aspect 59 is directed to the composition of Aspects 1 to 58, wherein less than about 20% of the lipid nanoparticles are emulsion particles.

[0087] Aspect 60 is directed to the composition of Aspects 1 to 59, wherein less than about 10% of the lipid nanoparticles are emulsion particles.

[0088] Aspect 61 is directed to the composition of Aspects 1 to 60, having a turbidity of about 0 to about 5000 Nephelometric Turbidity Units (NTU) at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[0089] Aspect 62 is directed to the composition of Aspects 1 to 61, having a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[0090] Aspect 63 is directed to the composition of Aspects 1 to 62, having a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[0091] Aspect 64 is directed to the composition of Aspects 1 to 63, having a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[0092] Aspect 65 is directed to the composition of Aspects 1 to 64, having a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for about 1 month at a relative humidity of about 75%.

[0093] Aspect 66 is directed to the composition of Aspects 1 to 65, wherein the composition does not include a sterol and/or a triglyceride. [0094] Aspect 67 is directed to the composition of Aspects 1 to 66, wherein the composition is free of synthetic surfactants and is free of synthetic emulsifiers at concentrations greater than about l/10^th that of phosphatidylcholine.

[0095] Aspect 68 is directed to the composition of Aspect 67, wherein the composition comprises less than about 2.5 wt. % of emulsifiers other than phosphatidylcholine.

[0096] Aspect 69 is directed to the composition of Aspects 1 to 68, wherein the composition is configured such that, upon storage for a period of one month at room temperature, the average size of the nanoparticles changes by less than about 20%.

[0097] Aspect 70 is directed to the composition of Aspects 1 to 69, wherein polydispersity index (PDI) of the plurality of nanoparticles in the composition is about 0.01 to about 0.8.

[0098] Aspect 71 is directed to the composition of Aspects 1 to 70, wherein PDI of the plurality of nanoparticles in the composition is about 0.05 to about 0.5.

[0099] Aspect 72 is directed to the composition of Aspects 1 to 70, wherein PDI of the plurality of nanoparticles in the composition is about 0. 1 to about 0.5.

[00100] Aspect 73 is directed to an aqueous formulation comprising the composition of any one of claims 1 to 72.

[00101] Aspect 74 is directed to the aqueous formulation of Aspect 73, wherein the composition is comprised in a second composition, and does not settle or separate from the second composition when stored for at least one month at a temperature of about 4 °C to about 20 °C.

[00102] Aspect 75 is directed to the aqueous formulation of Aspects 73 to 74, comprising 20 wt. % to about 99.0 wt. % of the lipid nanoparticles.

[00103] Aspect 76 is directed to the aqueous formulation of Aspects 73 to 75, comprising 50 wt. % to about 95.0 wt. % of the lipid nanoparticles.

[00104] Aspect 77 is directed to the aqueous formulation of Aspects 73 to 76, comprising 60.0 wt. % to about 80.0 wt. % of the lipid nanoparticles.

[00105] Aspect 78 is directed to the aqueous formulation of Aspects 73 to 74, comprising 8.0 wt. % to about 30.0 wt. % of the lipid nanoparticles.

[00106] Aspect 79 is directed to the aqueous formulation of Aspect 78, comprising 17.0 wt. % to about 21.0 wt. % of the lipid nanoparticles.

[00107] Aspect 80 is directed to the aqueous formulation of Aspects 73 to 79, having a turbidity of about 0 to about 5000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%. [00108] Aspect 81 is directed to the aqueous formulation of Aspects 73 to 80, having a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[00109] Aspect 82 is directed to the aqueous formulation of Aspects 73 to 81, having a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[00110] Aspect 83 is directed to the aqueous formulation of Aspects 73 to 82, wherein the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

[00111] Aspect 84 is directed to the aqueous formulation of Aspects 73 to 83, wherein the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for 1 month at a relative humidity of about 75%.

[00112] Aspect 85 is directed to the aqueous formulation of Aspects 73 to 84, wherein the aqueous formulation does not settle or separate when stored for at least one month at a temperature of about 20 °C.

[00113] Aspect 86 is directed to the aqueous formulation of Aspects 73 to 85, wherein the aqueous formulation is configured such that, upon storage for a period of one month at room temperature, the average size of the plurality of nanoparticles changes by less than about 20%. [00114] Aspect 87 is directed to the aqueous formulation of Aspects 73 to 86, wherein polydispersity index (PDI) of the plurality of nanoparticles in the aqueous formulation is about 0.01 to about 0.8.

[00115] Aspect 88 is directed to the aqueous formulation of Aspects 73 to 87, wherein PDI of the plurality of nanoparticles in the aqueous formulation is about 0.05 to about 0.5.

[00116] Aspect 89 is directed to the aqueous formulation of Aspects 73 to 88, wherein PDI of the plurality of nanoparticles in the aqueous formulation is about 0. 10 to about 0.5.

[00117] Aspect 90 is directed to the aqueous formulation of Aspects 73 to 89, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 20 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles. [00118] Aspect 91 is directed to the aqueous formulation of Aspects 73 to 90, wherein the aqueous formulation maintains aturbidity (EBC) of less than about 15 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00119] Aspect 92 is directed to the aqueous formulation of Aspects 73 to 91, wherein the aqueous formulation maintains aturbidity (EBC) of less than about 10 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00120] Aspect 93 is directed to the aqueous formulation of Aspects 73 to 92, wherein the aqueous formulation maintains aturbidity (EBC) of less than about 7 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00121] Aspect 94 is directed to the aqueous formulation of Aspects 73 to 93, wherein the aqueous formulation maintains aturbidity (EBC) of less than about 4 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00122] Aspect 95 is directed to the formulation of Aspects 73 to 94, wherein the aqueous formulation maintains a turbidity of less than about 2.5 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00123] Aspect 96 is directed to the aqueous formulation of Aspects 73 to 95, wherein the aqueous formulation maintains aturbidity of less than about 1 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00124] Aspect 97 is directed to the aqueous formulation of Aspects 73 to 96, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 300% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00125] Aspect 98 is directed to the aqueous formulation of Aspects 73 to 97, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 250% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00126] Aspect 99 is directed to the aqueous formulation of Aspects 73 to 98, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 200% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00127] Aspect 100 is directed to the aqueous formulation of Aspects 73 to 99, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 150% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00128] Aspect 101 is directed to the aqueous formulation ofAspects 73 to 100, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 125% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00129] Aspect 102 is directed to the aqueous formulation ofAspects 73 to 101, wherein the aqueous formulation maintains a turbidity of less than about 115% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00130] Aspect 103 is directed to the aqueous formulation of Aspects 73 to 102, wherein the aqueous formulation maintains a turbidity of less than about 110% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00131] Aspect 104 is directed to the aqueous formulation of Aspects 73 to 103, wherein the aqueous formulation maintains a turbidity (EBC) that does not significantly differ from the turbidity (EBC) of a control second composition over 5 days at about 40 °C with about 75% relative humidity, wherein the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of nanoparticles.

[00132] Aspect 105 is directed to an ingestible composition comprising the composition of any one of claims 1 to 72.

[00133] Aspect 106 is directed to the ingestible composition of Aspect 105, wherein the ingestible composition is a beverage.

[00134] Aspect 107 is directed to the ingestible composition of Aspects 105 to 106, comprising at least about 50.0 wt. % water.

[00135] Aspect 108 is directed to the ingestible composition of Aspects 105 to 107, wherein the ingestible composition is a fermented beverage.

[00136] Aspect 109 is directed to the ingestible composition of Aspects 105 to 108, wherein the ingestible composition is a carbonated beverage.

[00137] Aspect 110 is directed to the ingestible composition of Aspects 105 to 109, wherein ingestible composition is a beer.

[00138] Aspect 111 is directed to the ingestible composition of Aspect 110, wherein the composition or aqueous composition reduces the formation of acetyl aldehyde or beta- damascenone in the beer.

[00139] Aspect 112 is directed to the ingestible composition of Aspects 105 to 111, wherein the composition does not include alcohol.

[00140] Aspect 113 is directed to the ingestible composition of Aspects 105 to 112, wherein the composition includes alcohol.

[00141] Aspect 114 is directed to the ingestible composition of Aspect 113, wherein the composition comprises about 0.01 wt. % to about 10.0 wt % alcohol.

[00142] Aspect 115 is directed to the ingestible composition of Aspect 114, wherein the composition comprises about 2.0 wt. % to about 9.0 wt. % alcohol.

[00143] Aspect 116 is directed to the ingestible composition of Aspect 115, wherein the composition comprises about 3.0 wt. % to about 8.0 wt. % alcohol.

[00144] Aspect 117 is directed to the ingestible composition of Aspects 105 to 116, wherein the composition comprises an aqueous formulation and the plurality of the nanoparticles.

[00145] Aspect 118 is directed to the ingestible composition of Aspects 105 to 117, wherein the ingestible composition comprises about 10 to about 20 milligrams of the plurality of nanoparticles per about 1 gram of the ingestible composition. [00146] Aspect 119 is directed to the ingestible composition of Aspects 105 to 118, wherein the turbidity of the composition is not perceivable to the unaided eye.

[00147] Aspect 120 is directed to the ingestible composition of Aspects 105 to 119, wherein the pH of the composition is about 2.5 to 9.5.

[00148] Aspect 121 is directed to the ingestible composition of Aspects 105 to 120, wherein the pH of the composition is about 5.5 to about 7.5.

[00149] Aspect 122 is directed to the ingestible composition of Aspects 105 to 121, wherein the pH of the composition is about 6.0 to about 7.0.

[00150] Aspect 123 is directed to the ingestible composition of Aspects 105 to 122, wherein the pH of the composition is about 6.3 to about 6.7.

[00151] Aspect 124 is directed to a method of making the ingestible composition of any one of claims 105 to 123, the method comprising combining the composition of any one of claims 1 to 72 with an ingestible item.

[00152] Aspect 125 is directed to the method of Aspect 124, wherein the ingestible item is a beverage.

[00153] Aspect 126 is directed to the method of Aspect 125, wherein the beverage is a beer. [00154] Aspect 127 is directed to the method of Aspects 124 to 126, wherein the ingestible composition comprises about 10 to about 20 milligrams of the plurality of nanoparticles per about 1 gram of the ingestible item.

[00155] Aspect 128 is directed to a method of ingesting the ingestible composition of any one of claims 105 to 123 by a subject, the method comprising ingesting the ingestible composition.

[00156] Aspect 129 is directed to the method of Aspect 128, wherein ingesting the ingestible composition prevents or treats cancer in the subject.

[00157] Aspect 130 is directed to the method of Aspects 128 to 129, wherein ingesting the ingestible composition prevents or treats inflammation in the subject.

[00158] Aspect 131 is directed to the method of Aspects 128 to 130, wherein ingesting the ingestible composition reduces low-density lipoprotein levels and/or increases high-density lipoprotein levels in the subject.

[00159] Aspect 132 is directed to the method of Aspects 128 to 131, wherein ingesting the ingestible composition aids in recovery from a SARS-CoV-2 infection in the subject.

[00160] Aspect 133 is directed to a method of preserving a perishable composition, the method comprising combining the composition of any one of claims 1 to 72 to the perishable composition, wherein the composition preserves the perishable composition. [00161] Aspect 134 is directed to the method of Aspect 133, wherein the perishable composition is an ingestible composition.

[00162] Aspect 135 is directed to the method of Aspect 133, wherein the perishable composition is a topical skin composition.

[00163] Aspect 136 is directed to a topical skin care composition comprising the composition of any one of claims 1 to 72.

[00164] Aspect 137 is directed to the topical skin care composition of Aspect 136, wherein the topical skin care composition is an emulsion.

[00165] Aspect 138 is directed to the topical skin care composition of Aspect 137, wherein the emulsion is an oil-in-water emulsion.

[00166] Aspect 139 is directed to the topical skin care composition of Aspects 136 to 138, wherein the topical skin care composition comprises at least about 50.0 wt. % water.

[00167] Aspect 140 is directed to the topical skin care composition of Aspects 136 to 139, wherein the plurality of nanoparticles is comprised within an aqueous phase of the topical skin care composition.

[00168] Aspect 141 is directed to a method of applying the topical skin care composition of any one of claims 136 to 140 to skin, the method comprising applying the topical skin care composition to the skin.

[00169] Aspect 142 is directed to the method of Aspect 141, further comprising treating a skin condition.

[00170] Aspect 143 is directed to the method of Aspect 142, wherein the skin condition is a fine line, a wrinkle, uneven skin tone, hyperpigmented skin, or inflamed skin.

[00171] Aspect 144 is directed to the method of Aspects 141 to 143, wherein the topical skin care composition reduces skin inflammation.

[00172] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the disclosure, and vice versa. Furthermore, compositions of the disclosure can be used to achieve methods of the disclosure. [00173] Other objects, features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[00174] FIG. 1 depicts a graph showing the stability of formulations described herein in a carbonated non-alcoholic beverage. The graph depicts the stability of a lipid nanoparticle over time (in an accelerated aging protocol) as a function of turbidity (EBC) in compositions comprising xanthohumol (XTH) and vitamin D3. Lipid particles comprising xanthohumol or vitamin D3 were disposed within 330 mL of a carbonated beverage (e.g., non-alcoholic lager) for a final concentration of 0.19 mg D3 and 5 mg xanthohumol, 0.125 mg D3 and 15 mg xanthohumol, 0. 19 mg D3 and 5 mg xanthohumol, or 0. 125 mg D3 and 15 mg xanthohumol.

[00175] FIGS. 2A-2C, depict graphs showing the stability of formulations described herein comprising the flavonoid xanthohumol in carbonated beverages (e.g., carbonated alcoholic or non-alcoholic beverages). 2A) is a graph showing the stability of a lipid nanoparticle composition described herein comprising H90 phospholipids, and xanthohumol at 5 mg/330 mL or 15 mg/330 mL over time (X axis, days at 38 °C) as a function of turbidity (Y axis, NTU), when the composition was disposed within 330 mL of an alcoholic carbonated beverage (e.g., alcoholic lager). 2B) is a graph showing the stability of a lipid nanoparticle composition described herein comprising 85G phospholipids, and xanthohumol at 5 mg/330 mL or 15 mg/330 mL over time (X axis, days at 38 °C) as a function of turbidity (Y axis, NTU), when the composition was disposed within 330 mL of a non-alcoholic carbonated beverage (e.g., non-alcoholic lager). 2C) is a graph showing the stability of a lipid nanoparticle composition described herein comprising H90 phospholipids, and xanthohumol at 5 mg/330 mL or 15 mg/330 mL over time (X axis, days at 38 °C) as a function of turbidity (Y axis, NTU), when the composition was disposed within 330 mL of a non-alcoholic carbonated beverage (e.g., non-alcoholic lager).

[00176] FIGS. 3A-3L depict graphs showing the chemical stability of aqueous concentrate formulations described herein comprising the flavonoid xanthohumol. Formulations were stored at 25 °C with 60% relative humidity (RH), or 40 °C at 75% RH for at least 90 or 180 days.

[00177] FIGS. 4A-4J depict graphs showing the chemical stability of aqueous concentrate formulations described herein comprising the flavonoid xanthohumol in alcoholic beer. Beers were stored at 25 °C with 60% relative humidity (RH), or 40 °C at 75% RH for at least 90 days. [00178] FIGS. 5A-5J depict graphs showing the stability (particle size & PDI) of aqueous concentrate formulations described herein comprising the flavonoid xanthohumol. Formulations were stored at 25 °C with 60% relative humidity (RH), or 40 °C at 75% RH for at least 180 days. DETAILED DESCRIPTION

[00179] Applicant has found that compositions as described herein can provide stable nanoparticles capable of carrying a broad range of compounds of interest, such as active agents, hydrophobic compounds, hydrophilic compounds, plant extracts, etc. In some instances the nanoparticles are made of only natural materials (e.g., do not contain compounds that are not found in nature). In some instances, the nanoparticles may stay stable over months of storage, may stay in suspension over months of storage, and/or may reduce degradation of the compounds of interest as compared to the compounds of interest not in a nanoparticle or in a different nanoparticle. In some instances, the concentration of the compound of interest may be higher than that which is achievable with other nanoparticle formulations or in an aqueous solution without a nanoparticle. In some instances, the nanoparticles may be in two or more different forms of nanoparticles (e.g., liposome, micelle, nanoemulsion, multi-lamellar, double liposome, solid lipid particles). In some instances, the nanoparticles are simpler to produce, such as requiring no or less microfluidization or high pressure homogenization.

I. Definitions

[00180] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter belongs. The terminology used in the description of the subject matter herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the subject matter.

[00181] The use of the word “a” or “an” when used in conjunction with the term “comprising” may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[00182] The phrase “and/or” means “and” or “or”. To illustrate, A, B, and/or C includes: A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C. In other words, “and/or” operates as an inclusive or.

[00183] The words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. When used in the context of a compound, composition or device, the term “comprising” means that the compound, composition or device includes at least the recited features or components, but may also include additional features or components.

[00184] The compositions and methods for their making or use can “comprise,” “consist essentially of,” or “consist of’ any of the ingredients or steps disclosed throughout the specification. Compositions and methods “consisting essentially of’ any of the ingredients or steps disclosed limits the scope of the claim to the specified materials or steps which do not materially affect the basic and novel characteristic of the claimed disclosure. The phrase “consisting of’ excludes any element not specified.

[00185] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter belongs. The terminology used in the description of the subject matter herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the subject matter.

[00186] The terms “treatment,” “treating,” “treat” and the like shall be given its ordinary meaning and shall also include herein to generally refer to obtaining a desired pharmacologic and/or physiologic effect. The effect may be prophylactic in terms of completely or partially preventing a disorder, disease, or symptom thereof and/or may be therapeutic in terms of a partial or complete stabilization or cure for a disorder or disease and/or adverse effect attributable to the disorder or disease. “Treatment” shall also cover any treatment of a disorder or disease in a mammal, particularly a human, and includes: (a) preventing the disorder, disease, or symptom (e.g., of the disorder or disease) from occurring in a subject which may be predisposed to the disorder, disease, or symptom but has not yet been diagnosed as having it; (b) inhibiting the disorder, disease, or symptom, e.g., arresting its development; and/or (c) relieving the disorder, disease, or symptom (e.g., causing regression of the disorder, disease, or symptom).

[00187] The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. In addition, various adjuvants such as are commonly used in the art may be included. Considerations for the inclusion of various components in pharmaceutical compositions are described, e.g., in Gilman et al. (Eds.) (1990); Goodman and Gilman’s: The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press, which is incorporated herein by reference in its entirety.

[00188] The term “pharmaceutically acceptable salt” refers to salts that retain the biological effectiveness and properties of a compound, which are not biologically or otherwise undesirable for use in a pharmaceutical. In many cases, the compounds herein are capable of forming acid and/or base salts by virtue of the presence of amino and/or carboxyl groups or groups similar thereto. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, ascorbic acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like; particularly preferred are the ammonium, potassium, sodium, calcium and magnesium salts. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. Many such salts are known in the art, as described in US4783443A, Johnston et al., published September 11, 1987 (incorporated by reference herein in its entirety).

[00189] An “effective amount” or a “therapeutically effective amount” as used herein can refer to an amount of a therapeutic agent that is effective to relieve, to some extent, or to reduce the likelihood of onset of, one or more of the symptoms of a disease or condition (e.g., disorder), and includes curing a disease or condition. An “effective amount” or a “therapeutically effective amount” refers to that amount of a recited compound and/or composition that imparts a modulating effect, which, for example, can be a beneficial effect, to a subject afflicted with a disorder, disease or illness, including improvement in the condition of the subject (e.g., in one or more symptoms), delay or reduction in the progression of the condition, prevention or delay of the onset of the disorder, and/or change in clinical parameters, disease or illness, etc., as would be well known in the art. For example, an effective amount can refer to the amount of a composition, compound, or agent that improves a condition in a subject by at least 5%, e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%. In some embodiments, an improvement in a condition can be a reduction in disease symptoms or manifestations (e.g., pain, anxiety & stress, seizures, malaise, inflammation, mood disorders, insomnia, etc.). Actual dosage levels of active ingredients in an active composition of the presently disclosed subject matter can be varied so as to administer an amount of the active compound(s) that is effective to achieve the desired response for a particular subject and/or application. The selected dosage level will depend upon a variety of factors including, but not limited to, the activity of the composition, composition, route of administration, combination with other drugs or treatments, severity of the condition being treated, and the physical condition and prior medical history of the subject being treated. In some embodiments, a minimal dose is administered, and dose is escalated in the absence of dose-limiting toxicity to a minimally effective amount. Determination and adjustment of an effective dose, as well as evaluation of when and how to make such adjustments, are contemplated herein.

[00190] “Curing” means that the symptoms of a disease or condition are eliminated; however, certain long-term or permanent effects may exist even after a cure is obtained (such as extensive tissue damage).

[00191] ‘ ‘Treat” or “treating” or “treatment” refers to any type of action that imparts a modulating effect, which, for example, can be a beneficial effect, to a subject afflicted with a disorder, disease or illness, including improvement in the condition of the subject (e.g., in one or more symptoms), delay or reduction in the progression of the condition, and/or change in clinical parameters, disease or illness, curing the illness, etc.

[00192] The “patient” or “subject” treated as disclosed herein is, in some embodiments, a human patient, although it is to be understood that the principles of the presently disclosed subject matter indicate that the presently disclosed subject matter is effective with respect to all vertebrate species, including mammals, which are intended to be included in the terms “subject” and “patient.” Suitable subjects are generally mammalian subjects. The subject matter described herein finds use in research as well as veterinary and medical applications. The term “mammal” as used herein includes, but is not limited to, humans, non-human primates, cattle, sheep, goats, pigs, mini-pigs (a mini-pig is a small breed of swine weighing about 35 kg as an adult), horses, cats, dog, rabbits, rodents (e.g., rats or mice), monkeys, etc. Human subjects include neonates, infants, children, juveniles, adults and geriatric subjects. The subject can be a subject “in need of’ the methods disclosed herein can be a subject that is experiencing a disease state and/or is anticipated to experience a disease state, and the methods and compositions of the invention are used for therapeutic and/or prophylactic treatment.

[00193] As used herein, the term “weight percent” (or wt. %, weight %, percent by weight, etc.), when referring to a component, is the weight of the component divided by the weight of the composition that includes the component, multiplied by 100%. For example, the weight percent of component A when 5 grams of component A is added to 95 grams of component B is 5% (e.g., 5 g A / (5 g A + 95 g B) x 100%).

[00194] As used herein, the “dry weight %” (e.g., “dry wt. %”, “dry weight percent”, etc.) of an ingredient is the weight percent of that ingredient in the composition where the weight of water has not been included in the calculation of the weight percent of that ingredient. A dry weight % can be calculated for and includes either a composition that does not include water (e.g., that has been dried to, for example, a powder) or for a composition that includes water but where the amount of water is not included in the calculation.

[00195] As used herein, the “wet weight %” (e.g., “wet wt. %”, “wet weight percent”, etc.) of an ingredient is the weight percent of that ingredient in a composition where the weight of water is included in the calculation of the weight percent of that ingredient. For example, the dry weight percent of component A when 5 grams of component A is added to 95 grams of component B and 100 grams of water is 5% (e.g., 5 g A / (5 g A + 95 g B) x 100%). Alternatively, the wet weight percent of component A when 5 grams of component A is added to 95 grams of component B and 100 grams of water is 2.5% (e.g., 5 g A / (5 g A + 95 g B + 100 g water) x 100%).

[00196] As used herein, the term “weight volume percent” (or weight volume percentage, w/v, w/v (%), etc.), when referring to a component, is the weight of the component in grams divided by the volume of a solution in milliliters that includes the component, multiplied by 100%. For example, the w/v of component A when 5 grams of component A is added to a solution to provide 100 mb of solution is 5 w/v (%) (e.g., 5 g solute A / 100 mb solution x 100%).

[00197] When referring to an amount present for one or more ingredients, the term “collectively or individually” (and variations thereof) means that the amount is intended to signify that the ingredients combined may be provided in the amount disclosed, or each individual ingredient may be provided in the amount disclosed. For example, if agents A and B are referred to as collectively or individually being present in a composition at a wt % of 5%, that means that A may be at 5 wt % in the composition, B may be at 5 wt % in the composition, or the combination of A and B may be present at a total of 5 wt % (A + B = 5 wt %). Alternatively, where both A and B are present, A may be at 5 wt % and B may be at 5 wt %, totaling 10 wt %.

[00198] When referring to the amount present for one or more ingredients, the terms “or ranges including and/or spanning the aforementioned values” (and variations thereof) is meant to include any range that includes or spans the aforementioned values. For example, when the wt % of an ingredient is expressed as “1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values,” this includes wt % ranges for the ingredient spanning from 1% to 20%, l% to 10%, l% to 5%, 5% to 20%, 5% to 10%, and 10% to 20%.

[00199] As used herein, the term “extract” means a compound or group of compounds that has been extracted from an extract source. For example, an extract source may be a plant (e.g., flavonoids, hops, hemp, cannabis, kratom, kava, Kanna, etc.) or a fungus (e.g., mushrooms, cordyceps, lion mane, reishi, chaga gano, psilocybin mushrooms, etc.). An extract may be extracted from the extract source as a full spectrum extract, a broad spectrum extract, a distillate, or an isolate. Full-spectrum extracts can be made a variety of different ways known in the art, including through pressure along (e.g., using a press, such as a rosin press), solvent extraction (using an appropriate solvent, such as, ethanol, ether, ethyl acetate, acetone, low and medium chain hydrocarbon solvents, etc.), supercritical CO2 extraction, and the like. Where solvent extraction is used, extract can be collected by removing the extraction solvent medium. Broad spectrum extracts are more refined than full spectrum extracts. Broad spectrum extracts may be made by further purifying full spectrum extracts, removing particular agents from full spectrum extracts, etc. Distillates may be made using methods known in the art, including extracting a full or broad spectrum extract and, optionally performing vacuum filtration to remove insoluble, and preforming a distillation. Alternatively, a distillate may be collected by directly subjecting a source to distillation conditions. An isolate is a single compound that has been isolated in a purified form (including substantially pure forms or pure form).

[00200] As used herein, a “therapeutic ingredient” is a compound or group of compounds provided within a composition or as a composition that provides a therapeutic benefit. A therapeutic ingredient in a particular composition may be an extract, a therapeutic agent, or a group of therapeutic agents.

[00201] As used herein, a “therapeutic agent” (or “active” or “active agent”) is a compound that provides a therapeutic benefit. One or more therapeutic agents may be combined to provide a therapeutic ingredient in a composition. [00202] As used herein, the “entourage effect” is a mechanism by which the combination of therapeutic agents in extracts or therapeutic ingredients act synergistically to modulate or treat a disease or disorder or exert a therapeutic benefit.

[00203] As used herein, the term “phospholipid” refers to a lipid having two hydrophobic fatty acid tails and a hydrophilic head comprising of a phosphate group.

[00204] As used herein, the term “short chain triglyceride” refers to tri-substituted triglycerides with fatty acids having aliphatic tails of 1 to 5 carbon atoms (1, 2, 3, 4, 5) and mixtures thereof.

[00205] As used herein, the term “medium chain triglyceride” refers to tri-substituted triglycerides with fatty acids having aliphatic tails of 6 to 12 carbon atoms (6, 7, 8, 9, 10, 11, 12) and mixtures thereof.

[00206] As used herein, the term “long chain triglyceride” refers to tri-substituted triglycerides with fatty acids having an aliphatic tail of greater than 13 carbon atoms (13, 14, 15, 16, 17, 18, 19, 20, or more) and mixtures thereof.

[00207] As used herein, the term “sterol” refers to a subgroup of steroids with a hydroxyl group at the 3 -position of the A-ring.

[00208] As used herein, the term “Cmax” is given its plain and ordinary meaning and refers to the maximum (or peak) plasma concentration of an agent after it is administered.

[00209] As used herein, the term “Tmax” is given its plain and ordinary meaning and refers to the length of time required for an agent to reach maximum plasma concentration after the agent is administered.

[00210] As used herein, the term “AUC” is given its plain and ordinary meaning and refers to the calculated area under the curve, referring to a plasma concentration-time curve (e.g., the definite integral in a plot of drug concentration in blood plasma vs. time.).

[00211] As used herein, “polydispersity” or “PDI” is used to describe the degree of nonuniformity of a size distribution of particles. Also known as the heterogeneity index, PDI is a number calculated from a two-parameter fit to the correlation data (the cumulants analysis). This index is dimensionless and scaled such that values smaller than 0.05 are mainly seen with highly monodisperse standards.

[00212] As used herein, an “amino acid” includes amino acids with natural amino acid side chains or non-natural amino acid side chains. As used herein, a “natural amino acid side chain” refers to the side-chain substituent of a naturally occurring amino acid. Naturally occurring amino acids have a substituent attached to the a-carbon. Naturally occurring amino acids include Arginine, Lysine, Aspartic acid, Glutamic acid, Glutamine, Asparagine, Histidine, Serine, Threonine, Tyrosine, Cysteine, Methionine, Tryptophan, Alanine, Isoleucine, Leucine, Phenylalanine, Valine, Proline, and Glycine. As used herein, a “non-natural amino acid side chain” refers to the side-chain substituent of a non-naturally occurring amino acid. Non-natural amino acids include P-amino acids ( ³ and p²), Homo-amino acids, Proline and Pyruvic acid derivatives, 3 -substituted Alanine derivatives, Glycine derivatives, Ring-substituted Phenylalanine and Tyrosine Derivatives, Linear core amino acids and N-methyl amino acids. Exemplary non-natural amino acids are available from Sigma- Aldridge, listed under “unnatural amino acids & derivatives.” See also, Travis S. Young and Peter G. Schultz, “Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon,” J. Biol. Chem. 2010285: 11039- 11044, which is incorporated by reference in its entirety.

[00213] As used herein, the term “hydrophobic”, “water insoluble”, or “insoluble in water”, or “not soluble in water”, or similar terms can refer to a chemical that has a water solubility below 0.1 g in 100 ml of water at 20 °C and 101.325 kPa of pressure. As used herein, the term “hydrophilic”, or “water soluble”, or “soluble in water”, or similar terms can refer to a chemical that has a water solubility at or above 1 g in 100 ml of water at 20 °C and 101.325 kPa of pressure. As used herein, the term “semi-soluble in water”, “water semi-soluble”, or “ semiinsoluble in water”, or “water semi -insoluble”, or similar terms can refer to a chemical that has a water solubility at 0.1 g in 100 ml ofwater at 20 °C and 101.325 kPa of pressure to below 1 g in 100 ml ofwater at 20 °C and 101.325 kPa of pressure. As used herein, the term “solubility” refers to the solubility of the ingredient or compound in question in pure solvent at 20 °C and 101.325 kPa of pressure unless otherwise noted.

[00214] Terms and phrases used in this application, and variations thereof, especially in the appended claims, unless otherwise expressly stated, should be construed as open ended as opposed to limiting. As examples of the foregoing, the term “including” should be read to mean “including, without limitation,” “including but not limited to,” or the like; the term “having” should be interpreted as “having at least;” the term “includes” should be interpreted as “includes but is not limited to;” the term “example” is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; and use of terms like “preferably,” “preferred,” “desired,” or “desirable,” and words of similar meaning should not be understood as implying that certain features are critical, essential, or even important to the structure or function of any embodiment disclosed herein, but instead as merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the disclosure. Likewise, a group of items linked with the conjunction “or” should not be read as requiring mutual exclusivity among that group, in some embodiments, but rather should be read as “and/or”.

[00215] The terms “approximately,” “about,” and “substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, in several embodiments, as the context may dictate, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than or equal to 10% of the stated amount. The term “generally” as used herein represents a value, amount, or characteristic that predominantly includes or tends toward a particular value, amount, or characteristic.

[00216] Conditional language used herein, such as, among others, “can,” “could,” “might,” “may,” “e.g.,” and the like, unless specifically stated otherwise or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and/or steps. Thus, such conditional language is not generally intended to imply that features, elements and/or steps are in any way required for one or more embodiments or that these features, elements and/or steps are included or are to be performed in any particular embodiment. The terms “comprising,” “including,” “having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term “or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term “or” means one, some, or all of the elements in the list.

[00217] Conjunctive language such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive language is not generally intended to imply that certain embodiments require the presence of at least one of X, at least one of Y, and at least one of Z.

[00218] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. The indefinite article “a” or “an” does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope. [00219] The section headings used herein are for organizational purposes only and are not to be construed as limiting the described subject matter in any way. All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose. When definitions of terms in incorporated references appear to differ from the definitions provided in the present teachings, the definition provided in the present teachings shall control. It will be appreciated that there is an implied “about” prior to the temperatures, concentrations, times, etc. discussed in the present teachings, such that slight and insubstantial deviations are within the scope of the present teachings herein. In this application, the use of the singular includes the plural unless specifically stated otherwise

II. Therapeutic Ingredients and Agents and Plant Extracts

[00220] Disclosed herein are therapeutic lipid-based particle products comprising therapeutic ingredients. In some instances, a therapeutic ingredient comprises ingredients that have been developed as a pharmaceutical drug. In some instances, a therapeutic ingredient comprises ingredients that have been developed as a natural supplement. In some instances, a therapeutic ingredient comprises vitamins. In some embodiments, anano-lipid delivery system is utilized to impart apparent aqueous solubility and deliverability to an otherwise practically water insoluble molecule. In some embodiments, as disclosed herein, attributes of some embodiments disclosed herein have been determined to be high quality and reproducible. Such reproducibility and low variations may allow the products to generate a reproducible certificate of analysis for different batches.

[00221] In certain embodiments, Therapeutic Ingredients and Agents can be selected from those described in US Patent No: 11,260,033, filed March 24, 2021, and granted March 1, 2022, which is hereby incorporated in its entirety for the purposes described herein.

[00222] In some embodiments, at least one therapeutic agent in the lipid-based particle composition (and/or combination of therapeutic agents provided in the lipid-based particle composition) has a room temperature solubility in MCT oil of less than 1 mg/g. In some embodiments, at least one therapeutic agent in the lipid-based particle composition (and/or combination of therapeutic agents provided in the lipid-based particle composition) has a room temperature solubility in water of less than 1 mg/g. In some embodiments, at least one therapeutic agent in the lipid-based particle composition (and/or combination of therapeutic agents provided in the lipid-based particle composition) is hydrophobic. In some embodiments, at least one therapeutic agent in the lipid-based particle composition (and/or combination of therapeutic agents provided in the lipid-based particle composition) is hydrophillic. In some embodiments, at least one therapeutic agent in the lipid-based particle composition (and/or combination of therapeutic agents provided in the lipid-based particle composition) is hydroneutral. In some embodiments, at least one therapeutic agent used to prepare a lipid-based particle composition has an aqueous solubility in pure water at room temperature, neutral pH, and atmospheric pressure of less than or equal to about: 0.05 mg/ml, 0.01 mg/ml, 0.012 mg/ml, 0.001 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the solubility of the at least one therapeutic agent (and/or the amount of the therapeutic that can be provided in an aqueous solution) used to prepare the compositions disclosed herein can be improved to equal to or greater than about: 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the solubility of the at least one therapeutic agent can be improved by at least about: 50%, 100%, 150%, 200%, 500%, 1000%, 10,000%, or ranges including and or spanning the aforementioned values. In some embodiments, the solubility is measured as an amount that can be suspended for longer than 30 days and or that can be dissolved in an aqueous solution at a concentration of at least 20 mg/ml.

[00223] In some embodiments, as disclosed herein, the therapeutic agent(s) is or may be synthetic. In some embodiments, as disclosed herein, the therapeutic agent(s) is or may be nonsynthetic. In some embodiments, as disclosed herein, the therapeutic agent(s) is or may be semi-synthetic (e.g., prepared through fermentation, etc.). In some embodiments, as disclosed herein, the therapeutic agent(s) is or may be a plant and/or fungal extract. In some embodiments, the therapeutic agent(s) is or may comprise a polyphenol. In some embodiments, the therapeutic agents(s) is or may comprise a flavonoid. In some embodiments, the therapeutic agent(s) is or may comprise xanthohumol. In some embodiments, the therapeutic agent(s) is or may comprise resveratrol. In some embodiments, the therapeutic agent(s) is or may comprise dihydromyricetin. In some embodiments, the therapeutic agent(s) is or may comprise mangiferin. In some embodiments, the therapeutic agent(s) is or may comprise ascorbic acid or a salt of ascorbic acid. In some embodiments, as disclosed herein, the therapeutic agent(s) is or may be a vitamin. In some embodiments, the therapeutic agent(s) is or may comprise vitamin D3 (e.g., cholecalciferol).

[00224] In some embodiments, the therapeutic ingredient is or may be a combination of synthetic and non-synthetic therapeutic agents. In some embodiments, as disclosed elsewhere herein, the therapeutic ingredient is a single compound (or is substantially pure single compound). In some embodiments, the therapeutic ingredient comprises a mixture of different compounds (e.g., comprises a full spectrum of compounds from an extract, a mixture of isolates, etc.). In some embodiments, the therapeutic ingredient is an extract or a mixture of extracts from one or more therapeutic agent sources. In some embodiments, the therapeutic ingredient is a distillate or a mixture of distillates from one or more therapeutic agent sources. [00225] In some embodiments, the therapeutic ingredient is a vitamin, nutrient, plant extract, nutraceutical, pharmaceutical, or other beneficial agents for delivery. In some instances, the therapeutic ingredient may be an analgesic, an anesthetic, an antibacterial agent, an anticonvulsant, an antidementia agent, an antidepressant, an antidote, a deterrent, a toxicologic agent, an antiemetic, an antifungal, an antigout agent, an anti-inflammatory agent, an antimigraine agent, an antimyasthenic agent, an antineoplastic agent, an antiparasitic agent, an antiparkinson agent, an antipsychotic, an antipasticity agent, an antiviral, an anxiolytic, a bipolar agent, a blood glucose regulator, a blood product, a blood modifier, a blood volume expander, a cardiovascular agent, a central nervous system agent, a dental agent, an oral agent, a dermatological agent, an enzyme replacement agent, an enzyme modifying agent, a gastrointestinal agent, a genitourinary agent, a hormonal agent, a hormone stimulant, a hormone replacement, a hormone modifying agent, a hormone suppressant, an immunological agent, an inflammatory bowel disease agent, a metabolic bone disease agent, an ophthalmic agent, an otic agent, a respiratory tract agent, a sedative, a hypnotic, a skeletal muscle relaxant, a therapeutic nutrient, a therapeutic mineral, and/or a therapeutic electrolyte. The hormonal agent, a hormone stimulant, a hormone replacement, a hormone modifying agent, and/or hormone suppressant may act on the adrenal system, the pituitary system, the prostaglandin system, sex hormone, the thyroid, and/or the parathyroid.

[00226] In some embodiments, the therapeutic ingredient may comprise a small molecule. In some embodiments, the therapeutic ingredient may comprise a biologic. In some embodiments, the therapeutic ingredient may comprise a biomolecule. In some embodiments, the therapeutic ingredient may comprise a macromolecule. In some embodiments, the therapeutic ingredient may comprise a nucleic acid, a protein, a lipid, a carbohydrate, or a combination thereof. In some embodiments, the therapeutic ingredient may comprise a cell or a derivative of a cell. In some embodiments, the therapeutic ingredient may comprise antisense RNA. In some embodiments, the therapeutic ingredient may comprise an siRNA, a miRNA, a IncRNA, or a combination thereof. In some embodiments, the therapeutic ingredient may comprise a nucleic acid vector.

[00227] In some embodiments, a therapeutic ingredient may comprise an active compound (e.g., therapeutic agent) selected from the group comprising a Flavonoid, Dihydromyrciten, a Vitamin, CoQlO, an Omega 3 fatty acid, Huperzine A, Bacopa monnieri extract, Cannabidiol, Cannabigerol, Cannabinol, Cannabichromene, Tetrahydrocannabivarin, Tetrahydrocannabinol, Full extracts of hemp, Specific ratios of isolated cannabinoids, Cannabigerolic acid, Cannabidolic acid, Mitragynine, Payantheine, Mitraphylline, Speciociliantine, Speciogynine, Cholecalciferol, Ergocalciferol, D,L-Alpha-Tocopherol, Menaquinone, Ascorbyl palmitate, Retinyl palmitate, Beta-Sitosterol, Plant Sterol Rich Extracts, Cholesterol, Ubiquinone, Phosphatidylcholine, Phosphatidylserine, Eicosapentaenoic/Docosahexaenoic Acid Mixtures, Oleic Acid, Conjugated Linoleic Acid, Capric Triglycerides, Caprylic Triglycerides, Capric and Caprylic Triglyceride mixtures, Peppermint, Orange, Lemon Oils, Lutein, Kavain, Methysticin, Yangonin, Dihydromethysticin, and/or derivatives thereof.

[00228] In some embodiments, when formulated, the dry weight % of one or more therapeutic agents present in the composition is equal to or at least about: 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values. In some embodiments, the therapeutic agents are provided in an aqueous composition. In some embodiments, the wet weight % of the one or more therapeutic agents present in the composition (with water included) is equal to or at least about: 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more therapeutic agents may be provided in the wet composition at a concentration of greater than or equal to about: 0.01 mg/ml, 0.05 mg/ml, 0.1 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, 150 mg/ml, 200 mg/ml, or ranges including and/or spanning the aforementioned values.

[00229] In some embodiments, the one or more therapeutic agents used in the lipid-based particle compositions as disclosed herein has high purity as indicated by its existing in a solid form (e.g., powder) prior to processing (e.g., formulation into a composition as disclosed herein). In some embodiments, using the combinations disclosed herein, a composition comprising one or more therapeutic agents in an aqueous solution is provided. In some embodiments, the delivery system may be lipid-based and forms an oil-in-water emulsion (e.g., a nanoemulsion), a liposome, and/or solid lipid particle (e.g., nanoparticle). In some embodiments, the lipid-based delivery system provides particles in the nano-measurement range (as disclosed elsewhere herein). In some embodiments, a solid lipid nanoparticle is spherical or substantially spherical nanoparticle. In some embodiments, a solid lipid nanoparticle possesses a solid lipid core matrix that can solubilize lipophilic molecules. In some embodiments, the lipid core is not stabilized by surfactants and/or emulsifiers beyond a phospholipid. In some embodiments, surfactants are absent. In some embodiments, the size of the particle is measured as a mean diameter. In some embodiments, the size of the particle is measured by dynamic light scattering. In some embodiments, the size of the particle is measured using a zeta-sizer. In some embodiments, the size of the particle can be measured using Scanning Electron Microscopy (SEM). In some embodiments, the size of the particle is measured using a cryogenic SEM (cryo-SEM). Where the size of a nanoparticle is disclosed elsewhere herein, any one or more of these instruments or methods may be used to measure such sizes.

[00230] In some embodiments, as disclosed elsewhere herein, the lipid-based particle and/or nanoparticle composition, or simply the composition for brevity, comprises a therapeutic agent or combination of therapeutic agents, a plant extract, and one or more phospholipid. In some embodiments, as disclosed elsewhere herein, the composition comprises, consists of, or consists essentially of therapeutic agent or combination of therapeutic agents, a phospholipid, a plant extract, an optional bulking agent, an optional buffer, an optional solvent, and/or an optional preservative. In some embodiments, the composition is aqueous (e.g., contains water) while in other embodiments, the composition is dry (lacks water or substantially lacks water). In some embodiments, the composition has been dried (e.g., has been subjected to a process to remove most or substantially all water). In some embodiments, the composition comprises nanoparticles in water (e.g., as a solution, suspension, or emulsion). In other embodiments, the composition is provided as a powder (e.g., that can be constituted or reconstituted in water). In some embodiments, as disclosed elsewhere herein, the water content (in wt %) of the composition is less than or equal to about: 25%, 20%, 15%, 10%, 5%, 2.5%, 1%, 0.5%, 0.1%, or ranges including and/or spanning the aforementioned values.

[00231] As disclosed elsewhere herein, in some embodiments, the lipid-based particle composition may include one or more therapeutic agents (e.g., a single therapeutic agent or a combination of therapeutic agents) as a therapeutic ingredient. In some embodiments, the lipid- based particle composition may include a single therapeutic agent or a plurality of therapeutic agents (e.g., 1, 2, 3, 4, or more). In some embodiments, the lipid-based particle composition may include a single therapeutic extract or a plurality of therapeutic extracts (e.g., 1, 2, 3, 4, or more).

[00232] In some embodiments, the therapeutic agents, collectively or individually, are present in the aqueous lipid-based particle composition at a concentration of less than or equal to about: 250 mg/mL, 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more therapeutic agents, collectively or individually, are present in the aqueous composition at a concentration of greater than or equal to about: 250 mg/mL, 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more therapeutic agents, collectively or individually, are present in the composition at a dry wt % of equal to or at least about: 0.001%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more therapeutic agents, collectively or individually, are present in the composition at a wet wt. % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder (that is free of or substantially free of water). In some embodiments, where the composition has been dried, it comprises a water content of less than or equal to 20%, 15%, 10%, 7.5%, 5%, 2.5%, 1%, or ranges including and/or spanning the aforementioned values.

[00233] In some embodiments, the therapeutic ingredient may comprise, consist of, or consist essentially of a full spectrum or broad spectrum plant/fungal extract. In some embodiments, the therapeutic ingredient may comprise, consist of, or consist essentially of a specific highly pure plant/fungal extract (e.g., a flavonoid, e.g., a prenylated flavonoid, e.g., xanthohumol). In some embodiments, a therapeutic ingredient may improve the functionality of a lipid-particle described herein.

[00234] In some embodiments, the therapeutic agent is one or more of a vitamin, a nutrient, a plant extract, a nutraceutical, a pharmaceutical, or another beneficial agent. In some embodiments, the therapeutic agent is hydrophilic. In some embodiments, the therapeutic agent is hydrophobic. In some embodiments, the therapeutic agent (e.g., non-cannabinoid therapeutic) is amphiphilic.

[00235] In several embodiments, the active ingredients provided in the nanoparticle composition may comprise, in addition to the plant extract of the composition, another extract that is an active agent. The plant extracts can be an unenriched extract (e.g., a mixture of agents as extracted from a single plant source), an enriched extract that has been enriched through purification processes (to have larger amounts of certain active agents), or any individual active component of the extract (e.g., a pure or substantially pure compound). As an example, the nanoparticle composition may include an unenriched extract that is isolated by bulk extraction of multiple actives from a plant biomass at one time. Alternatively, the nanoparticle composition may include actives that have been further processed to enrich the extract for particular active agents (e.g., having a higher wt. % of the active agent than un-processed extract). In several embodiments, alternatively, an active from an extract may be purified and may be pure and/or substantially pure, as disclosed elsewhere herein. For brevity, when a composition or particle disclosed herein is described as including plant extracts, the term “extracts” is meant to include any of the foregoing (e.g., including a full plant extract or partial plant extract that has not been enriched, an extract that has been enriched for particular components (e.g., particular active agents), and/or an extract that has been purified to provide, for example, highly pure individual components). In some instances, the plant extract is enriched in glycosides by the extraction. In some instances, the plant extract comprises at least, at most, between, at, or any range thereof of 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, or 99 wt. % glycosides. In some instances, the plant extract is enriched in terpenoid glycosides. In some instances, the plant extract comprises at least, at most, between, at, or any range thereof of 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, or 99 wt. % terpenoid glycosides. In some instances, the plant extract is a deoiled plant extract. In some instances, the plant extract has had oil at least 50% of the oil removed, 60% removed, 70% removed, 80% removed, 90% removed, 95% removed, 98% removed, 99% removed, 100% removed, etc. In some instances, the plant extract comprises an extract of Tribulus terrestris, Yucca schidigera, Quillaja saponaria, Camillia sinesis, and/or Glycyrrhiza glabra.

[00236] Tribulus terrestris, also known as puncture vine or caltrop, is a taprooted herbaceous annual plant adapted to dry and temperate climates. In some instances, Tribulus terrestris extract is commercially available, e.g. from JK Botannicals and PureBulk, Inc. Yucca schidigera, also known as Mojave yucca, is a flowering evergreen tree native to North American deserts. In some instances, Yucca schidigera extract are commercially available. Quillaja saponaria, also known as quillaja or soapbark, is an evergreen tree native to Chile. In some instances, Quillaja saponaria extract are commercially available. Camillia sinesis, also known as tea plant, tea shrub, or tea tree, is an evergreen shrub commonly used to produce black and green tea. In some instances, Camillia sine sis extract is commercially available, e.g. from Shaanxi Huike Botanical Development Co., Ltd and Herb-Key. Glycyrrhiza glabra, also known licorice, is an herbaceous perennial legume used in consumables, pharmaceuticals, cosmetics, and medicine. In some instances, Glycyrrhiza glabra extract are commercially available.

[00237] In some embodiments, the plant extract used has a significant concentration of saponins present. In some instances, the saponin content of the plant extract is greater than about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 98%, or about 99%. In some embodiments, the plant extract consists of saponins. In some embodiments, a saponin is used in addition to or in replacement of a plant extract. In some embodiments, when formulated, the dry weight % of one or more saponins present in the composition is equal to or at least about: 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values. In some embodiments, the saponins are provided in an aqueous composition. In some embodiments, the wet weight % of the one or more saponins present in the composition (with water included) is equal to or at least about: 0.000001%, 0.000005%, 0.00001%, 0.00005%, 0.0001%, 0.0005%, 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more saponins may be provided in the wet composition at a concentration of greater than or equal to about: 0.000001 mg/ml, 0.000005 mg/ml 0.00001 mg/ml, 0.00005 mg/ml 0.0001 mg/ml, 0.0005 mg/ml 0.001 mg/ml, 0.005 mg/ml, 0.01 mg/ml, 0.05 mg/ml, 0.1 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, 150 mg/ml, 200 mg/ml, or ranges including and/or spanning the aforementioned values.

[00238] In some embodiments, the therapeutic agent is selected from the group consisting ofNoopept (N-phenylacetyl-L-prolyglygice ethyl ester), a flavonoid, a vitamin (e.g., vitamin D, e.g., vitamin D3), melatonin, glutathione, gamma-glutamylcysteine (GGC), gamma- aminobutyric acid (GABA), valerian root, magnesium, theanine, 5-HTP, tyrosine, taurine, zinc, alpha fenchone, alpha terpinene, alpha terpineol, beta caryophyllene, alpha pinene, beta pinene, bisabolene, bisabolol, borneol, eucalyptol, gamma terpinene, guaiacol, humulene, linalool, myrcene, para cymene, phytol, terpinolene, limonene, others, and/or combinations thereof. In some embodiments, when a hydrophilic composition is used, it is mixed with the aqueous soluble ingredients before mixing with the lipid ingredients.

[00239] In some embodiments the lipid particles comprise extracts of mushrooms (e.g., cordyceps, lion mane, reishi, chaga gano, psilocybin (including the compound itself, natural extract forms, synthetic forms, derivatives of psilocybin, and prodrugs of any one of the foregoing), others, and/or combinations of any of the foregoing), kratom extracts, Kanna extracts, kava extracts, or combinations of any one or more of the foregoing.

[00240] In some embodiments, the compounds (e.g., therapeutic agents) are derived from or are broad spectrum extracts (e.g., oils, etc.), full spectrum extracts (e.g., oils, etc.), distillates (e.g., oils, etc.), and/or combinations thereof. In some embodiments, the lipid particles are composed of or comprise compounds (e.g., therapeutic agents) from a crude extract (an extract that is not further purified). In some embodiments, the lipid particle is composed of compounds (e.g., therapeutic agents) from combinations of sources.

[00241] In some embodiments, an active compound comprises at least one antioxidant. Nonlimiting examples of antioxidants that can be used with the compositions of the present invention include acetyl cysteine, ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butyl hydroquinone, cysteine, cysteine HCI, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters of ascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters, hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural botanical anti-oxidants such as green tea or grape seed extracts, nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide, thiodigly colic acid, thiogly colic acid, thiolactic acid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50, tocopherol, tocophersolan, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate, and tris(nonylphenyl)phosphite .

[00242] In some embodiments, the active compound comprises at least one essential oil. Essential oils include oils derived from herbs, flowers, trees, and other plants. Such oils are typically present as tiny droplets between the plant’s cells, and can be extracted by several methods known to those of skill in the art (e.g., steam distilled, enfleurage, maceration, solvent extraction, or mechanical pressing). When these types of oils are exposed to air they tend to evaporate. As a result, many essential oils are colorless, but with age they can oxidize and become darker. Essential oils are insoluble in water and are soluble in alcohol, ether, fixed oils (vegetal), and other organic solvents. Typical physical characteristics found in essential oils include boiling points that vary from about 160 to 240 °C and densities ranging from about 0.759 to about 1.096.

[00243] Essential oils typically are named by the plant from which the oil is found. For example, rose oil or peppermint oil are derived from rose or peppermint plants, respectively. Non-limiting examples of essential oils that can be used in the context of the present invention include sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, pimento berries oil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil, lemon oil, lemongrass oil, lime oil, mandarin oil, maijoram oil, myrrh oil, neroli oil, orange oil, patchouli oil, pepper oil, black pepper oil, petitgrain oil, pine oil, rose otto oil, rosemary oil, sandalwood oil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, or ylang. Other essential oils known to those of skill in the art are also contemplated as being useful within the context of the present invention.

[00244] In some embodiments, the active agent comprises an algae extract. The algae extract may comprise ashwagandha and/or astoxantin.

[00245] In some embodiments, the active compound is encapsulated by particle at a concentration of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270,

280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460,

470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650,

660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840,

850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700,

2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200,

4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700,

5800, 5900, 6000, 6100, 6200, 6300, 6400, 6500, 6600, 6700, 6800, 6900, 7000, 7100, 7200,

7300, 7400, 7500, 7600, 7700, 7800, 7900, 8000, 8100, 8200, 8300, 8400, 8500, 8600, 8700,

8800, 8900, 9000, 9100, 9200, 9300, 9400, 9500, 9600, 9700, 9800, 9900, or 10000 mg, or ranges including and/or spanning the aforementioned values, per kg of the nanoparticle and/or a composition comprising the nanoparticle.

[00246] In some embodiments, the active compound comprises a flavonoid. In some embodiments, the active compound comprises a prenylated (e.g., comprise a lipophilic prenyl side-chain) flavonoid. In some embodiments, a prenylated flavonoid is a chaicone, dihydrochalcone, flavone, flavanone, flavonol, and/or isoflavone. In some embodiments, a prenylated flavonoid comprises C-prenylation and/or O-prenylation. In some embodiments, a flavonoid may be a bioflavonoid, isoflavonoid, and/or neoflavonoid. In some embodiments, a flavonoid may be an anthocyanidin, chaicone, flavonol, flavanone, flavan-3-ol, flavanonol, flavone, and/or isoflavonoid.

[00247] In some embodiments, a chaicone may be, but is not limited to: xanthohumol, Flavokawin, Butein, Xanthoangelol, 4-Hydroxyderricin, Cardamonin, 2', 'Dihydroxy chaicone, Isoliquiritigenin, Isosalipurposide, and/or Naringenin chaicone.

[00248] In some embodiments, a flavanol may be, but is not limited to: a Flava-3-ol, Catechin, Gallocatechin, Catechin 3 -gallate, Gallocatechin 3 -gallate, Epicatechins, Epigallocatechin, Epicatechin 3 -gallate, Epigallocatechin 3 -gallate, a Flavan-4-ol, a Flavan- 3,4-diol, Leucoanthocyanidin, and/or a Proanthocyanidin.

[00249] In some embodiments, a flavone may be, but is not limited to: Luteolin, Apigenin, Tangeretin, a Flavanol, a Quercetin, Quercitrin, Rutin, a Kaempferol, Kaempferitrin, Astragalin, Naringenin, Sophoraflavonoloside, Myricetin, Fisetin, Isorhamnetin, Pachypodol, Rhamnazin, a Flavanone, Hesperetin, Hesperidin, Eriodictyol, Homoeriodictyol, a Flavanonol, Taxifolin, Dihydroquercetin, and/or Dihydrokaempferol.

[00250] In some embodiments, an Anthocyanidin may be, but is not limited to: Anthocyanidin, Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, and/or Petunidin.

[00251] In some embodiments, an Isoflavonoid may be, but is not limited to: a Phytoestrogen, a Isoflavone, Genistein, Daidzein, Glycitein, an Isoflavane, Equol, Lonchocarpane, and/or Laxiflorane.

[00252] In some embodiments, a Neoflavonoid may be, but is not limited to: a Neoflavone, Calophyllolide, a Neoflavene, Dalbergichromene, Coutareagenin, Dalbergin, and/or Nivetin. [00253] In some embodiments, a flavonoid is xanthohumol. In some embodiments, xanthohumol may be comprised in an extract that comprises one or more additional hop derived chemicals.

[00254] In some embodiments, the flavonoid is highly pure. In some embodiments, compositions provided herein comprise two or more sources of flavonoids. In some embodiments, compositions provided herein comprise two or more sources of prenylflavonoids. In some embodiments, the flavonoid has a purity by weight % of equal to or greater than about: 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or ranges including and/or spanning the aforementioned values.

[00255] In some embodiments, a flavonoid is about 70% to about 90% pure. In some embodiments, a flavonoid is at a concentration of about 300 to about 600 grams per liter in density. In some embodiments, a flavonoid comprises less than about, equal to about, or greater than about 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, or 20% concentration of other prenylflavonoids.

[00256] In some embodiments, aflavonoid is greaterthan about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or 95% pure. In some embodiments, a flavonoid is greater than about 90% pure. In some embodiments, a flavonoid is at a concentration of about 200 to 400 grams per liter in density. In some embodiments, a flavonoid comprises less than about, equal to about, or greater than about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% concentration of other prenylflavonoids.

[00257] In some embodiments, a flavonoid is about 65 to about 85% pure. In some embodiments, a flavonoid is at a concentration of about 150 to about 300 grams per liter in density. In some embodiments, a flavonoid comprises less than about, equal to about, or greater than about 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, or 30% concentration of other prenylflavonoids. In some embodiments, a flavonoid is Isoxanthohumol. In some embodiments, a flavonoid is not Isoxanthohumol.

[00258] In some embodiments, a flavonoid comprises, consists essentially of, or consists of XANTHOFLAV™ by HOPSTEINER (S.S. STEINER, INC., NY, USA). In some embodiments, a xanthohumol comprises, consists essentially of, or consists of XANTHOFLAV™ by HOPSTEINER (SS. STEINER, INC., NY, USA). In some embodiments, a flavonoid comprises, consists essentially of, or consists of XANTHOFLAV™ PURE by HOPSTEINER (S.S. STEINER, INC., NY, USA). In some embodiments, a high purity xanthohumol comprises, consists essentially of, or consists of XANTHOFLAV™ PURE by HOPSTEINER (SS. STEINER, INC., NY, USA). In some embodiments, a flavonoid comprises, consists essentially of, or consists of ISO-XANTHOFLAV by HOPSTEINER (S.S. STEINER, INC., NY, USA). In some embodiments, the flavonoid xanthohumol is comprised in XANOHOP™ and/or XANOHOP™ GOLD by BETATEC (BETATEC HOP PRODUCTS, Washington DC, USA).

III. Particles

[00259] In some embodiments, as disclosed elsewhere herein, a lipid-based particle composition is provided to aid in the delivery of therapeutic agents. In some embodiments, the lipid-based particle composition (e.g., when in water or dried) comprises multilamellar particle vesicles, unilamellar particle vesicles, and/or emulsion particles. In some embodiments, the composition is characterized by having multiple types of particles (e.g., multilamellar, unilamellar, emulsion, etc.). In some embodiments, a majority of the particles present are emulsion particles. In some embodiments, a majority of the particles present are lamellar (multilamellar and/or unilamellar). In some embodiments, a majority of the particles are unilamellar. In some embodiments, a minority of the particles present are emulsion particles. In some embodiments, a minority of the particles present are multilamellar.

[00260] In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 75%, 85%, or 95%, (or ranges spanning and/or including the aforementioned values) are multilamellar nanoparticle vesicles. In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% (or ranges spanning and/or including the aforementioned values) are multilamellar nanoparticle vesicles. For example, in some embodiments, between about 5% and about 10% of the particles present are multilamellar. In some embodiments, of the particles present more are unilamellar than are multilamellar.

[00261] In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%,

12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%,

28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%,

44%, 45%. 46%. 47%, 4^%. 49%, 50%. 5 1 %. 52%. 53%, 54%, 55%, 56%, 57%, 58%, 59%,

60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%,

76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,

92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% (or ranges spanning and/or including the aforementioned values) are unilamellar nanoparticle vesicles. In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% (or ranges spanning and/or including the aforementioned values) are unilamellar nanoparticle vesicles. For example, in some embodiments, between about 50% and 100%, or 50% and 90%, or 50% and 80%, or 50% and 70%, or 50% and 60%, of the particles present are unilamellar. In some embodiments, more of the particles present are unilamellar when compared to multilamellar. In some embodiments, a majority of the particles are unilamellar.

[00262] In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) are emulsion particles. In some embodiments, of the particles present in the composition (e.g., the aqueous composition), equal to or less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, (or ranges spanning and/or including the aforementioned values) are emulsion particles. For example, in some embodiments, between about 1% to about 20%, or about 1% to about 10%, of the particles present are emulsion particles.

[00263] In some embodiments, liposomes comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).

[00264] In some embodiments, micelle particles comprise equal to or less than about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition). In some embodiments, a composition does not comprise micelle particles.

[00265] In some embodiments, irregular particles comprise equal to or less than about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition). In some embodiments, a composition does not comprise irregular particles.

[00266] In some embodiments, combined lamellar and emulsion particles comprise equal to or at least about 5%, 6%, 7%, 8%, 9%, 10%, 15%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).

[00267] In some embodiments, mixed-micelle particles comprise equal to or less than about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition). In some embodiments, a composition does not comprise mixed-micelle particles. [00268] In some embodiments, the particle compositions can comprise combinations of multilamellar particles, unilamellar particles, emulsion particles, micelle particles, irregular particles, and/or liposomes. In some embodiments, the particle compositions can comprise or consist of combinations of multilamellar particles, unilamellar particles, and emulsion particles.

[00269] The percentages and/or concentrations of particles present in the composition may be purposefully modified. In some embodiments, the percentage and/or concentration of the particles present in the composition are tailored to the active compound and/or the liquid comprising the particles. Such tailoring may lead to more homogenization and/or dispersion in the liquid. The tailoring may stabilize dispersion in the liquid. Such tailoring may also tailor to specific densities of the compositions. The densities of the compositions can be matched or different from a liquid that the compositions are contacted by or contained within.

[00270] In some embodiments, the composition is biased towards one type of particle, such as solid particles or liposomes. The composition may be biased by increasing or decreasing the ratio in the composition of lipids that are solid at room temperature to lipids that are liquid at room temperature. Biasing the composition may alter characteristics of the composition including density, particle composition, solubility, pharmacokinetic properties, or other characteristics described herein. In some embodiments, the composition is biased towards unilamellar liposomes by increasing the concentration of lipids that are solid at room temperature (e.g., phosphatidylcholine).

[00271] In some embodiments, the composition is free of surfactants other than the phosphatidylcholine and those in the plant extract. In some embodiments, the composition is free of synthetic surfactants. A synthetic surfactant may be a surfactant that is not produced in nature. In some embodiments, the nanoparticle composition does not comprise a surfactant other than a phospholipid and/or a surfactant that is contained in the plant extract. In some embodiments, a composition is free of emulsifiers at concentrations greater than about 1/10^th that of phosphatidylcholine and/or emulsifiers in the plant extract. In some embodiments, a composition comprises less than about 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, or 10.0 wt. % of a surfactant and/or emulsifiers other than phosphatidylcholine and those in the plant extract.

[00272] In some embodiments, a composition comprises high purity triglycerides, such as oleic acid and/or conjugated linoleics. In some embodiments, the composition does not comprise high purity triglycerides. In some embodiments, the composition does not comprise medium chain triglycerides. In some instances, the composition does not comprise an oil. In some instances, the composition does not comprise more than 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01 wt. % of an oil. The composition may be formulated, such as by changing the composition or concentration of lipids, for specific delivery or specific metabolism. For example, the composition may comprise medium chain triglycerides to bias the composition towards phase 1 liver metabolism. In some embodiments, the composition is formulated for a specific absorption mechanism, such as lymphatic absorption or liver first pass.

IV. Phospholipids

[00273] As disclosed herein, the lipid-based particle composition comprises one or more phospholipids. In some embodiments, the one or more phospholipids comprises one or more of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, and phosphatidylinositol trisphosphate. In some embodiments, the phospholipid component is primarily phosphatidylcholine. In some embodiments, the only phospholipid present is phosphatidylcholine (e.g., the phospholipid lacks phospholipids other than phosphatidylcholine or is substantially free of other phospholipids). In some embodiments, the one or more phospholipid components (e.g., phosphatidylcholine, and/or others), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 600 mg/ml, 500 mg/ml, 400 mg/ml, 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 10 mg/ml, or ranges including and/or spanning the aforementioned values. For instance, in some embodiments where two or more phospholipids are present (e.g., phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, etc.), those phospholipids may be present collectively at a concentration of less than or equal to about: 600 mg/ml, 500 mg/ml, 400 mg/ml, 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 10 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a dry wt. % of equal to or less than about: 5%, 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a dry wt % of about 45% to about 90%, In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a dry wt % of about 53% to about 75%. In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a wet wt. % of equal to or greater than about: 1%, 2%, 3%, 4%, 5%, 6%, 7%, 7.5%, 8%, 9%, 10%, 11%, 12%, 12.5%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a wet wt. % of equal to or about 7.5% to about 25%. In some embodiments, the one or more phospholipid(s) (collectively or individually) are present in the composition at a wet wt. % of equal to or about 10% to about 20%. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the phosphatidylcholine is synthetic, derived from sunflower, soy, egg, or mixtures thereof. In some embodiments, the one or more phospholipids (and/or lipids) can be hydrogenated or non-hydrogenated. In some embodiments, a phosphatidylcholine is comprised in a phosphatidylcholine composition (e.g., a lecithin).

[00274] In some embodiments, where a phospholipid (e.g., phosphatidylcholine) is used, the phospholipid (e.g., phosphatidylcholine) may be of high purity. For example, in some embodiments, the high purity phosphatidylcholine is H100-3 grade (from Lipoid) and includes over 96.3% phosphatidylcholine (hydrogenated) or over 99% phosphatidylcholine (hydrogenated). In some embodiments, the high purity phosphatidylcholine composition is H90 lecithin (from Lipoid) and includes over 95% phosphatidylcholine (non-hydrogenated) (e.g., Table 2). In some embodiments, the high purity phosphatidylcholine composition is 85G lecithin (from Phospholipid GmbH) and includes over 94% phosphatidylcholine (non- hydrogenated) (e.g., Table 3). In some embodiments, the high purity phospholipid composition (e.g., phosphatidylcholine composition) has a purity of greater than or equal to about: 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 96.3%, 97%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values, for a specific phospholipid. In some embodiments, the phospholipid composition (e.g., phosphatidylcholine composition) has a total non-phospholipid % impurity content by weight of less than or equal to about: 30%, 25%, 20%, 17.5%, 15%, 12.5%, 10%, 9.5%, 9%, 8.5%, 8%, 7.5%, 7%, 6.5%, 6%, 5.5%, 5%, 4.5%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.5%, 0%, or ranges including and/or spanning the aforementioned values. In some embodiments, the phospholipid composition (e.g., phosphatidylcholine composition) comprises less than or equal to about 8.5%, 8%, 7.5%, 7%, 6.5%, 6%, 5.5%, 5%, 4.5%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.5%, 0%, (or ranges including and/or spanning the aforementioned values) of any one or more of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (C 18), arachidonic acid (ARA) (C 20:4), docosahexaenoic acid DHA (C 22:6), phosphatidic acid, phosphatidylethanolamine, and/or lysophosphatidylcholine by weight. In some embodiments, the phosphatidylcholine composition has less than about 1.1% lysophosphatidylcholine and less than about 2.0% triglycerides by weight. In some embodiments, a composition may comprise Lysophosphatidylcholine (1-LPC), 2-Lysophosphatidylcholine (2-LPC), Phosphatidylethanolamine (PE), N-acylphosphatidylethanolamine (APE), Phosphatidylinositol (PI), and/or Phosphatidic acid (PA). In some embodiments, the concentration of 1-LPC, 2-LPC, PE, APE, PI, and/or PA are at or below l/10^th the concentration of phosphatidylcholine.

[00275] In some embodiments, a phospholipid composition (e.g., phosphatidylcholine composition) may be of mixed purity. For example, in some embodiments, the phosphatidylcholine composition is H20 grade lecithin (from Lipoid), which is a mixed purity phosphatidylcholine composition, and includes approximately 37% phosphatidylcholine (hydrogenated), approximately 29% Phosphatidylinositol (PI), and approximately 16% Phosphatidylethanolamine (e.g., Table 1).

[00276] In some embodiments, a composition may comprise a mixture of at least two different phospholipid compositions (e.g., phosphatidylcholine compositions). In some embodiments, a composition may comprise a mixture of a high purity phospholipid composition (e.g., phosphatidylcholine composition) and a mixed purity phospholipid composition (e.g., phosphatidylcholine composition). In some embodiments, a composition may comprise a mixture of H20 lecithin (e.g., Table 1), and H90 lecithin (e.g., Table 2) phospholipids. In some embodiments, a composition may comprise a mixture of H20 lecithin (e.g., Table 1), and 85G lecithin (e.g., Table 3) phospholipids.

Table 1 - H20 lecithin phospholipid content

Table 2 - H90 lecithin phospholipid content

Table 3 - 85G lecithin phospholipid content

[00277] In certain embodiments, compositions disclosed herein do not comprise a sterol. In certain embodiments, compositions disclosed herein do not comprise detectable levels of a sterol. In certain embodiments, compositions disclosed herein do not comprise sterols at greater than 0.1 w/w%. In certain embodiments, compositions disclosed herein do not comprise triglycerides. In certain embodiments, compositions disclosed herein do not comprise detectable levels of a triglyceride. In certain embodiments, compositions disclosed herein do not comprise a triglyceride at greater than 0.1 w/w%. In certain embodiments, compositions disclosed herein do not comprise an oil. In certain embodiments, compositions disclosed herein do not comprise detectable levels of an oil. In certain embodiments, compositions disclosed herein do not comprise an oil at greater than 0. 1 w/w%. In certain embodiments, compositions disclosed herein do not comprise water. In certain embodiments, compositions disclosed herein do not comprise detectable levels of water. In certain embodiments, compositions disclosed herein do not comprise water at greater than 5 w/w%.

[00278] In some embodiments, a lipid-based particle composition comprises one or more sterols. In some embodiments, the one or more sterols comprises one or more cholesterols, ergosterols, hopanoids, hydroxysteroids, phytosterols (e.g., vegapure), ecdysteroids, and/or steroids. In some embodiments, the sterol comprises cholesterol. In some embodiments, the sterol is cholesterol. In some embodiments, the only sterol present is cholesterol (e.g., the sterol lacks or substantially lacks sterols other than cholesterol). In some embodiments, the one or more sterol(s) (e.g., cholesterol, and/or other sterols), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 100 mg/ml, 50 mg/ml, 40 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more sterol(s) are present in the composition at a dry wt. % of equal to or less than about: 0.001%, 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 40%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more sterol(s) (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the cholesterol used in the composition comprises cholesterol from one or more of sheep’s wool, synthetic cholesterol, or semisynthetic cholesterol from plant origin. In some embodiments, the sterol (or combination of sterols) has a purity of greater than or equal to about: 92.5%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 100.0%, or ranges including and/or spanning the aforementioned values. In some embodiments, the sterol has a total % impurity content by weight of less than or equal to about: 8.5%, 8%, 7.5%, 7%, 6.5%, 6%, 5.5%, 5%, 4.5%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.5%, 0%, or ranges including and/or spanning the aforementioned values. In some embodiments, the sterol is cholesterol. In some embodiments, the sterol is not cholesterol. In some embodiments, the sterol is phytosterol. V. Preservatives

[00279] In some embodiments, the lipid-based particle composition comprises a preservative. In some embodiments, the preservative includes one or more benzoates (such as sodium benzoate or potassium benzoate), nitrites (such as sodium nitrite), sulfites (such as sulfur dioxide, sodium or potassium sulphite, bisulphite or metabisulphite), sorbates (such as sodium sorbate, potassium sorbate), ethylenediaminetetraacetic acid (EDTA) (and/or the disodium salt thereof), polyphosphates, organic acids (e.g., citric, succinic, malic, tartaric, benzoic, lactic and propionic acids), and/or antioxidants (e.g., vitamins such as vitamin E and/or vitamin C, butylated hydroxytoluene). In some embodiments, the one or more preservatives, collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 10 mg/ml, 5 mg/ml, 1 mg/ml, 0.85 mg/ml, 0.5 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more preservatives (collectively or individually) are present in the composition at a dry wt. % of equal to or at less than about: 0.01%, 0.1%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more preservatives (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.025%, 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the aqueous composition comprises one or more of malic acid at about 0.85 mg/ml, citric acid at about 0.85 mg/ml, potassium sorbate at about 1 mg/ml, and sodium benzoate at about 1 mg/ml. In some embodiments, the preservatives inhibit or prevent growth of mold, bacteria, and fungus. In some embodiments, Vitamin E is added at 0.5 mg/ml to act as an antioxidant in the oil phase. In some embodiments, the preservative concentrations may be changed depending on the flavored oil used. In some embodiments, the preservative concentrations may be changed depending on the therapeutic ingredients used.

VI. Flavoring Agents and Dyes

[00280] In some embodiments, the lipid-based particle composition comprises one or more flavoring agents. In some instances, the one or more flavoring agents is an active agent. In some embodiments, the one or more flavoring agent(s), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more flavoring agent(s) (collectively or individually) are present in the composition at a dry wt. % of equal to or less than about: 0.01%, 0.1%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more flavoring agents (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.025%, 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the one or more flavoring agents of the composition comprise monk fruit extract (e.g., MonkGold50), stevia, peppermint oil, lemon oil, vanilla, or the like, or combinations thereof. In some embodiments, the composition contains MonkGold50 at 0.9 mg/ml and flavored oils as flavoring. Examples of flavored oils are peppermint and lemon at 1.2 mg/ml. Chemicals that are not oil may also be used for flavor, for example, such as dry powders that replicate a flavor such as vanilla. In some embodiments, a flavoring agent is and/or comprises maltodextrin.

[00281] In some embodiments, the lipid-based particle composition comprises one or more dyes (e.g., colorants). In some instances, the one or more dyes is an active agent. In some instances, the one or more dyes is not synthetic. In some embodiments, the one or more dye(s), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0. 1 mg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more dye(s) (collectively or individually) are present in the composition at a dry wt. % of equal to or less than about: 0.01%, 0. 1%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more dye(s) (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.025%, 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder.

[00282] In some instances, the dyes are not synthetic dyes. In some instances, the dyes are natural dyes. In some instances, the natural dyes include anthocyanins. In some instances, the dyes are more stable in the nanoparticles disclosed herein than in a similar nanoparticle that does not contain the plant extract. In some instances, the natural dye is a purple sweet potato extract, black carrot extract, red radish extract, red cabbage extract, grape extract, grape skin extract, aronia extract, elderberry extract, and/or hibiscus extract.

VII. Water Content

[00283] In some embodiments, the lipid-based particle composition is aqueous while in other embodiments the composition may be provided as a dry or substantially dry solid (e.g., having a water content in weight % of less than or equal to 25%, 20%, 15%, 10%, 5%, 2%, 1%, 0.5%, 0.1%, 0%, or ranges including and/or spanning the aforementioned values). In some embodiments, where the lipid-based particle composition is aqueous, water may be present at a wet weight percent of equal to or less than about: 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 77%, 80%, 85%, 90%, 95%, 97.5%, 99%, or ranges including and/or spanning the aforementioned values. In some instances where the composition is dry or substantially dry, water may be present at a wt. % of at, less than, between, or a range of 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or 0%. In some instances, the composition is a dry powder. In some instances, the nanoparticles are a dry powder.

VIII. Bulking Agents and Other Additives

[00284] In some embodiments, the lipid-based particle composition comprises one or more bulking agents (e.g., carbohydrates, polymers, etc.). In some embodiments, the lipid-based particle composition comprises one or more carbohydrates (and/or a carbohydrate source). In some embodiments, a bulking agent comprises a polymer. In certain embodiments, a bulking agent comprises acacia/Arabic gum. In some embodiments, a bulking agent comprises one or more types of fiber derived from one or more different sources. In some embodiments, the bulking agent is selected from the group consisting of a saccharide, an oligosaccharide, a polysaccharide, a monosaccharide, a protein, a lipid, trehalose, sucrose, dextrose, glucose, isomaltulose, tagatose, arabinose, maltose, fructose, dextrin, lactose, maltose, fucose, galactose, a gum, inositol, maltodextrin, maltol, mannose, muscovado, ribose, rhamnose, saccharose, sucralose, xylose, lecithin, fiber, avocado fiber, acacia fiber, psyllium fiber, betaglucan, guar gum, xanthan gum, pectin, chitin, cellulose, a modified cellulose, methylcellulose, hemicellulose, microcrystalline cellulose, beta cyclodextrin, an alginate salt, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, ammonium alginate, propylene glycol alginate, agar, carrageen, raffinose, polydextrose, cyclodextrins, fullerene, inulin, gelatin, pentose, and combinations and/or polymers thereof. In some embodiments, one or more bulking agents comprises polydextrose, inulin, FOS, resistant starch, and/or maltodextrins. In some embodiments, the one or more bulking agents, collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 400 mg/mL, 350 mg/mL, 300 mg/mL, 250 mg/mL, 200 mg/mL, 175 mg/mL, 150 mg/mL, 125 mg/mL, 100 mg/ml, 90 mg/ml, 80 mg/ml, 70 mg/ml, 60 mg/ml, 50 mg/ml, 40 mg/ml, 30 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more bulking agents (collectively or individually) are present in the composition at a dry wt. % of equal to or less than about: 0.001%, 0.01%, 0.1%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 35%, 50%, 60%, 70%, 80%, 90%, 95% or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more bulking agents (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.1%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, 15%, 20%, 30%, 40%, 50%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the one or more bulking agents, surprisingly, stabilize the lipid composition when in powdered form (e.g., dry or substantially dry form). In some embodiments, the one or more bulking agents surprisingly help the lipid composition to return to particle form (e.g., nano or microparticle form) when reconstituted.

[00285] In some embodiments, the lipid-based particle composition comprises one or more one or more other additives, such as amino acids, polyethylene glycols, etc. In some embodiments, the one or more additives, collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 400 mg/mL, 350 mg/mL, 300 mg/mL, 250 mg/mL, 200 mg/mL, 175 mg/mL, 150 mg/mL, 125 mg/mL, 100 mg/ml, 90 mg/ml, 80 mg/ml, 70 mg/ml, 60 mg/ml, 50 mg/ml, 40 mg/ml, 30 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more additives (collectively or individually) are present in the composition at a dry wt. % of equal to or less than about: 0.001%, 0.01%, 0.1%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 35%, 50%, 60%, 70%, 80%, 90%, 95% or ranges including and/or spanning the aforementioned values. In some embodiments, the one or more additives (collectively or individually) are present in the composition at a wet wt. % of equal to or less than about: 0.001%, 0.01%, 0.1%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, 15%, 20%, 30%, 40%, 50%, or ranges including and/or spanning the aforementioned values. In some embodiments, as disclosed elsewhere herein, the composition is aqueous, while in others it has been dried into a powder. In some embodiments, the one or more additives, surprisingly, stabilize the lipid composition when in powdered form (e.g., dry or substantially dry form). In some embodiments, the one or more additives surprisingly help the lipid composition to return to particle form (e.g., nano or microparticle form) when reconstituted.

IX. Exemplary Additional Therapeutics, Compositions, and Methods

[00286] In some embodiments, the lipid-based particle composition (e.g., when in water or dried) comprises multilamellar nanoparticle vesicles, unilamellar nanoparticle vesicles, multivesicular nanoparticles, and/or emulsion particles. In some embodiments, the composition is characterized by having multiple types of particles (e.g., multilamellar, unilamellar, and emulsion, etc.). In some embodiments, a majority of the particles present are lamellar (multilamellar and/or unilamellar) particles. In some embodiments, a majority of the particles present are unilamellar particles. In some embodiments, a minority of the particles present are emulsion particles.

[00287] In some embodiments, at ambient temperature an aqueous lipid-based composition as disclosed herein has a viscosity (in centipoise (cP)) of equal to or less than about: 1.0, 1.05, 1.1, 1.2, 1.5, 2.0, 5.0, 10.0, 20, 30, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, or ranges including and/or spanning the aforementioned values.

[00288] In some embodiments, the liposomes and/or a liquid (e.g., aqueous) composition comprising the nanoparticles as disclosed herein are lyophilized. In some embodiments, where lyophilization is used to prepare a liposomal- and/or nanoparticle-based powder, one or more lyoprotectant agents may be added. In some embodiments, an individual lyoprotectant agent may be present at a dry wt. % equal to or less than the dry weight of the lipophilic ingredients. In some embodiments, the lyoprotectant agent(s) (collectively or individually) may be present at a dry wt. % equal to or less than about: 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values. In some embodiments, the lyoprotectant agent(s) (collectively or individually) may be present at a wet wt % of equal to or less than about: 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, or ranges including and/or spanning the aforementioned values. In some embodiments, the lyoprotectant is selected from the group consisting of lactose, dextrose, trehalose, arginine, glycine, histidine, and/or combinations thereof. In several embodiments, the nanoparticle compositions herein are spray dried (e.g., to provide a powder). In several embodiments, the nanoparticle compositions are spray dried and not lyophilized. In some embodiments, the nanoparticle composition is spray dried, fluid bed dried, desiccated, and/or lyophilized. [00289] Nanoparticle formulations containing active agents can be formed into spray dried powders. Formulations containing active agents alone with varying amounts of various lipids and other excipients can be prepared using a solvent-free manufacturing process. Water-soluble components can be dissolved in water at 65 °C with magnetic stirring. High shear mixing can be applied at 65°C and lipids and excipients can be added. High shear mixing can be maintained until a stable suspension is formed. The suspension can then optionally be microfluidized for 1,2, 3, 4, or 5 passes using an MP110 microfluidizer at 5,000, 10,000, 15,000, 20,000, 25,000, or 30,000 psi. Following microfluidization, formulations can be diluted with an equal volume containing the excipient type such that the excipient is at the stated final concentration. Up to 25% ethanol (e.g., 10%, 15%, 20%, 25%) can be added to the formulation and mixed to a homogenous solution prior to spray drying. Formulations can be spray dried on a Buchi B290 benchtop spray dryer. The inlet temperature can be set at 125 °C, the aspirator set to 100%, the pump rate set to 10%, and nitrogen flow set to 60 mmHg. Powder can be collected and measured for residual moisture, and recovered yield can be calculated.

[00290] As disclosed elsewhere herein, some embodiments pertain to methods of preparing lipid-based particle compositions comprising nanoparticles and/or liposomes. In some embodiments, the composition is prepared by forming a lipid-in-oil emulsion. In some embodiments, an oil-in-water emulsion can be prepared without the use of organic solvents. In some embodiments, a composition can be prepared without the use of organic solvents. In some embodiments, a composition can be prepared in a solvent-free process. In some embodiments, solid ingredients are added and dissolved into liquid ingredients In some embodiments, the phospholipid composition (e.g., phosphatidylcholine composition) can be added with mixing. In some embodiments, when a well dispersed lipid phase is formed after mixing, the addition of water (e.g., having a temperature of equal to or at least about: 0. 1 °C, 1 °C, 5 °C, 10 °C, 20 °C, 30 °C, 40 °C, 50 °C, 60 °C, 80 °C, or ranges including and/or spanning the aforementioned values) and additional mixing achieves an oil-in-water emulsion. In some embodiments, the oil-in-water emulsion is then subject to high-shear mixing to form nanoparticles. In some embodiments, high-shear mixing is performed using a high shear dispersion unit or an in-line mixer can be used to prepare the emulsions. In some embodiments, the particles can be made by solvent evaporation and/or solvent precipitation. In some embodiments, the particles can be made in a solvent-free process. In some embodiments, the particles can be made in solvent- free process that does not comprise solvent evaporation and/or solvent precipitation.

[00291] In some embodiments, oil-in-water emulsion is subject to high-pressure homogenization using a microfluidizer. In some embodiments, high sheer mixing can be used to reduce the particle size. In some embodiments, the oil-in-water emulsion is processed to a nanoparticle (e.g., about 20 to about 500 nm, etc.) using the microfluidizer or other high sheer processes. In some embodiments, the oil-in-water emulsion is processed to a nanoparticle having a size from about 30 nm to about 200 nm in diameter, about 80 nm to about 180 nm in diameter, about 50 nm to about 150 nm in diameter, or about 100 nm to about 150 nm in diameter.

[00292] In some embodiments, an oil-in-water emulsion is passed through the microfluidizer a plurality of times (e.g., equal to or at least 1 time, 2 times, 3 times, 4 times, 5 times, 10 times, or ranges including and/or spanning the aforementioned values). In some embodiments, an oil-in-water emulsion is passed through the microfluidizer in discreet volumes per pass. In some embodiments, an oil-in-water emulsion is passed through the microfluidizer in non-discreet volumes in a continuous process. In some embodiments, an emulsion is passed through the microfluidizer at a pressure of equal to or less than about: 5,000 PSI, 15,000 PSI, 20,000 PSI, 25,000 PSI, 30,000 PSI, or ranges including and/or spanning the aforementioned values. In some embodiments, the emulsion is passed through the microfluidizer at a temperature of equal to or at least about: 30 °C, 40 °C, 50 °C, 65 °C, 80 °C, or ranges including and/or spanning the aforementioned values. In some embodiments, the emulsion is passed through the microfluidizer at least about room temperature (e.g., about 20 °C or about 25 °C) and/or without any heating and/or temperature control. In some embodiments, the emulsion is passed through the microfluidizer at a temperature of equal to or less than about 80 °C. In some embodiments, the microfluidizer includes an interaction chamber consisting of 75 pm to 200 pm pore sizes and the emulsion is passed through this chamber. In some embodiments, the pore size of the microfluidizer are less than or equal to about: 75 pm, 100 pm, 150 pm, 200 pm, 250 pm, 300 pm, or ranges including and/or spanning the aforementioned values. In some embodiments, the nanoparticle composition is prepared by high shear mixing, sonication, and/or extrusion.

[00293] In some embodiments, after preparation, the lipid-based particle composition is characterized by an ability to pass through a 0.2 pm filter while preserving the nanoparticle structure (e.g., a change in average nanoparticle size of no greater than 10 nm, 20 nm, or 30 nm). In some embodiments, after passage through a 0.2 pm there is a change in average diameter of the particles of equal to or at less than about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values. In some embodiments, after passage through a 0.2 pm there is a change in PDI of the particles of equal to or at less than about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values. [00294] In some embodiments, as disclosed elsewhere herein, the lipid-based particle composition is composed of highly pure ingredients, including but not limited to GMP grade therapeutic agents and/or GMP grade phospholipids. In some embodiments, the composition (and/or one or more ingredients constituting the compositions) is manufactured with high purity, multicompendial ingredients to be at the same standards as pharmaceutical products. In some embodiments, the composition is manufactured using pharmaceutical equipment and documentation to ensure the product is of high quality and consistent from batch to batch.

[00295] In some embodiments, advantageously, the nanoparticle delivery systems disclosed herein are reproducibly manufacturable. In some embodiments, the method of manufacture of the compositions avoids the introduction of contaminants (such as metal contamination).

[00296] In some embodiments, over 50%, 75%, 90%, 95%, 99% (or ranges spanning and or including the aforementioned values) of the nanoparticles disclosed herein have a particle size of between about 20 to about 500 nm (as measured by zeta sizing (e.g., refractive index)). In some embodiments, over 50%, 75%, 90%, 95%, 99% (or ranges spanning and or including the aforementioned values) of the nanoparticles disclosed herein have a particle size of between about 50 nm to about 200 nm (as measured by zeta sizing (e.g., refractive index)). In some embodiments, over 50%, 75%, 90%, 95%, 99% (or ranges spanning and or including the aforementioned values) of the nanoparticles disclosed herein have a particle size of between about 50 nm to about 150 nm (as measured by zeta sizing (e.g., refractive index)). In some embodiments, over 50%, 75%, 90%, 95%, 99% (or ranges spanning and or including the aforementioned values) of the nanoparticles disclosed herein have a particle size of at least 100 nm (as measured by zeta sizing (e.g., refractive index). In some embodiments, this consistency in size allows predictable delivery to subjects.

[00297] In some embodiments, the lipid-based delivery system described herein offers protection to therapeutic agents against degradation in an aqueous environment for long-term storage. In some embodiments, the composition is well characterized to ensure a consistent product from batch to batch and with long-term stability. In some embodiments, the product stability is routinely tested for appearance, particle size and distribution, zeta potential, residual solvents, heavy metals, therapeutic agent concentration, and microbial testing and the values measured using these test methods varies (over a period of at least about 1 month or about 6 months at 25 °C with 60% relative humidity) by less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values. In some embodiments, the particle size and/or PDI varies over a period of at least about 1 month or about 6 months (e.g., at 4 °C with uncontrolled humidity, at 25 °C with 60% relative humidity, and/or at 40 °C with 75% relative humidity) by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. As noted elsewhere herein, PDI and size can be measured using conventional techniques. In some embodiments, the therapeutic agent concentration (i.e., chemical stability) varies over a period of at least about 1 month or about 6 months (e.g., at 4 °C with uncontrolled humidity, at 25 °C with 60% relative humidity, and/or at 40 °C with 75% relative humidity) by less than or equal to about: 1%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. As noted elsewhere herein, chemical stability can be measured using conventional techniques.

[00298] In some embodiments, the formulations and/or compositions disclosed herein are stable during sterilization. In some embodiments, the sterilization may include one or more of ozonation, UV treatment, and/or heat treatment. In some embodiments, the particle size and/or PDI after sterilization (e.g., exposure to techniques that allow sterilization of the composition) varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, the therapeutic agent concentration after sterilization (e.g., exposure to techniques that allow sterilization of the composition) varies (e.g., drops) by less than or equal to about: 1%, 5%, 10%, 15%, or ranges including and/or spanning the aforementioned values. [00299] In some embodiments, the lipid-based particle compositions (including after stabilization) disclosed herein have a shelf life of equal to or greater than 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, or ranges including and/or spanning the aforementioned values. The shelf life can be determined as the period of time in which there is 95% confidence that at least 50% of the response (therapeutic agent(s) concentration or particle size) is within the specification limit. This refers to a 95% confidence interval and when linear regression predicts that at least 50% of the response is within the set specification limit.

[00300] In some embodiments, the lipid-based particle composition contains preservatives to protect against bacteria, mold, and fungal growth. In some embodiments, over a period of about 1 month, about 6 months, or about 12 months the composition has equal to or not more than: 50 cfii/gram, 10 cfii/gram, 5 cfii/gram, 1 cfii/gram, 0.1 cfii/gram, or ranges including and/or spanning the aforementioned values. In some embodiments, 1 week at 20 °C - 25 °C after a 10⁵-10⁷ CFU/mL challenge with any one of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus brasiliensis the composition has equal to or not more than: 100 cfu/gram, 50 cfu/gram, 25 cfu/gram, 10 cfu/gram, 5 cfu/gram, 1 cfu/gram, 0.1 cfu/gram, or ranges including and/or spanning the aforementioned values. In some embodiments, 1 week at 20 °C - 25 °C after a 10⁵- 10⁷ CFU/mL challenge with any one of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus brasiliensis the composition has a log reduction for the bacteria of equal to or greater than: 1, 2, 3, 4, 5, 10, or ranges including and/or spanning the aforementioned values.

[00301] In some embodiments, advantageously, the individual particles within the disclosed lipid-based particle compositions may not settle or sediment appreciably. In some embodiments, an appreciable amount of the composition (e.g., as viewed by the naked eye) does not settle and/or separate from an aqueous liquid upon standing. In some embodiments, the composition does not appreciably settle or separate from an aqueous liquid upon standing for equal to or at least about 1 day, at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, or ranges including and/or spanning the aforementioned values. In some embodiments, upon standing, the composition remains dispersed in an aqueous liquid for at least about 1 day, at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, or ranges including and/or spanning the aforementioned values. In some embodiments, the homogeneity of the disclosed compositions changes by equal to or less than about: 0.5%, 1%, 5%, 7.5%, 10%, or 15% (or ranges including and/or spanning the aforementioned values) after a period of one week or one month. In this case, homogeneity is observed through images by SEM or cryo- SEM (e.g., the average size of the particles and/or the particle types). In some embodiments, the composition remains dispersed in an aqueous liquid and does not appreciably settle or separate from an aqueous liquid after at least about: 1 minute, 5 minutes, 30 minutes, or an hour in a centrifuge at a centripetal acceleration of at least about 100 m/s, at least about 1000 m/s, or at least about 10,000 m/s. In some embodiments, the composition remains dispersed in an aqueous liquid and does not appreciably settle or separate from an aqueous liquid after at least about: 1 minute, 5 minutes, 30 minutes, or an hour in a centrifuge at a centrifuge speed of 5000 RPM, 10,000 RPM, or 15,000 RPM.

[00302] In some embodiments, as disclosed elsewhere herein, the nanoparticle delivery system aids in absorption of the therapeutic agent when orally ingested and/or topically applied. In some embodiments, the compositions disclosed herein allow the therapeutic agent to be delivered to and/or absorbed through the gut and/or the skin. As disclosed elsewhere herein, some embodiments pertain to the use of the lipid-based nanodelivery system to protect the therapeutic agent from degradation and/or precipitation in the aqueous solution it is stored in (e.g., in an aqueous composition for administration to a subject). In some embodiments, use of the delivery systems disclosed herein result in improved bioavailability and/or absorption rate. For instance, in some embodiments, the Cmax of a therapeutic is increased using a disclosed embodiment, the Tmax of is decreased using an embodiment as disclosed herein, and/or the AUC is increased using a disclosed embodiment.

[00303] In some embodiments, the pharmacokinetic outcomes disclosed elsewhere herein (Cmax, Tmax, AUC, ti/2, etc.) can be achieved using aqueous lipid-based particle compositions or powdered lipid-based particle compositions (e.g., where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.).

[00304] In some embodiments, the Cmax of the therapeutic agent or ingredient is increased using the disclosed embodiments relative to other delivery vehicles (e.g., after administration to a subject). In some embodiments, the Cmax is increased relative to the therapeutic agent or ingredients alone or comparator embodiments (e.g., oil-based products) by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, the therapeutic agent Cmax is increased (relative to a comparator oil-based product) by equal to or at least about: 5%, 10%, 20%, 30%, 50%, 100%, or ranges including and/or spanning the aforementioned values. In some embodiments, the therapeutic agent Cmax is increased (relative to a comparator oil-based product) by equal to or at least about: 10 ng/mL, 20 ng/mL, 30 ng/mL, 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, or ranges including and/or spanning the aforementioned values.

[00305] In some embodiments, the Cmax for a disclosed embodiment is increased relative to an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, these pharmacokinetic results can be achieved using aqueous compositions or powdered compositions (where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.). In some instances, the Cmax using a disclosed embodiment is 1.25 times higher than when using a comparator delivery system (e.g., the Cmax of the comparator x 1.25). In some instances, the Cmax using a disclosed embodiment is equal to or at least about 1.25 times higher, 1.5 times higher, 2 times higher, 3 times higher (or ranges including or spanning the aforementioned values) than when using a comparator delivery system.

[00306] Advantageously, in some embodiments, a composition disclosed herein may achieve a more steady release of therapeutic. This may be reflected by a lower Cmax when compared to some comparator compositions. In some embodiments, the Cmax for a disclosed embodiment is decreased relative to an equal dose of a therapeutic agent in an comparator vehicle. In some embodiments, the Cmax for a disclosed embodiment is decreased relative to a comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, these pharmacokinetic results can be achieved using aqueous compositions or powdered compositions (where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.). In some instances, the Cmax using a disclosed embodiment is 1.25 times lower than when using a comparator delivery system. In some instances, the Cmax using a disclosed embodiment is equal to or at least about 1.25 times lower, 1.5 times lower, 2 times lower, 3 times lower (or ranges including or spanning the aforementioned values) than when using a comparator delivery system.

[00307] In some embodiments, the Tmax for a therapeutic agent using a disclosed embodiment is shortened relative to other vehicles. In some embodiments, after a dose of therapeutic agent provided in an embodiment as disclosed herein to a subject as disclosed herein, the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values. In some embodiments, after a dose (e.g., of 15 mg/kg) of therapeutic agent provided in an embodiment as disclosed herein to a subject, the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values. In some embodiments, after a dose of therapeutic agent provided in an embodiment as disclosed herein to a subject, the Tmax is between about 4 hours and about 6.5 hours or between about 3 hours and about 7 hours. In some embodiments, after a dose of 15 mg of therapeutic agent provided in an embodiment as disclosed herein to a human patient, the Tmax is equal to or less than about: 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.

[00308] In some embodiments, the Tmax for the therapeutic agent using a disclosed embodiment is improved relative to oil-based vehicles (e.g., has a shorter duration to Tmax). In some embodiments, using an embodiment as disclosed herein, the Tmax is shortened relative to comparable delivery vehicles (e.g., an oil-based vehicle) by equal to or at least about: 5%, 10%, 15%, 20%, 25%, 50%, or ranges including and/or spanning the aforementioned values. In some embodiments, the Tmax is shortened relative to the therapeutic agent(s) alone by equal to or at least about: 5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In some embodiments, the Tmax for a disclosed embodiment is decreased relative to an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, the Tmax of a therapeutic agent for a disclosed embodiment is decreased relative to an oil-based comparator vehicle by equal to or at least about: 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, or ranges including and/or spanning the aforementioned values. In some instances, the Tmax is a fraction of that achieved using a comparator delivery system. In some instances, the time to Tmax using a disclosed embodiment is 0.5 times, 0.7 times, 0.8 times, 0.9 times, or 0.95 times the Tmax of a comparator delivery system (or ranges including or spanning the aforementioned values).

[00309] In some embodiments, after of a dose of therapeutic agent or ingredient (provided in an embodiment as disclosed herein to a subject (e.g., a mini-pig, human, etc.), the AUC is equal to or at least about: 50 ng/mL*hr, 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, 450 ng/mL*hr, 500 ng/mL*hr, 550 ng/mL*hr, 600 ng/mL*hr, 650 ng/mL*hr, 700 ng/mL*hr, 800 ng/mL*hr, 1000 ng/mL*hr, or ranges including and/or spanning the aforementioned values.

[00310] In some embodiments, the AUC for a therapeutic agent using a disclosed embodiment is increased (relative to a therapeutic agent itself or a comparator delivery vehicle) by equal to or at least about: 50 ng/mL*hr, 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, or ranges including and/or spanning the aforementioned values. In some embodiments, the AUC using a disclosed embodiment is increased (relative to a therapeutic agent itself or a comparator delivery vehicle) by equal to or at least about: 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values. In some embodiments, the AUC is improved relative to a therapeutic agent alone or in an oil mixture by equal to or at least about: 5%, 25%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some instances, the AUC using a disclosed embodiment is 1.25 times higher than when using a comparator delivery system. In some instances, the AUC using a disclosed embodiment is equal to or at least about 1.25 times higher, 1.5 times higher, 2 times higher, 3 times higher (or ranges including or spanning the aforementioned values) than when using a comparator delivery system. [00311] In some embodiments, the half-life for a therapeutic agent (ti/2) in vivo using a disclosed embodiment can be shorter relative to other vehicles. In some embodiments, after a dose of therapeutic agent provided in an embodiment as disclosed herein to a subject as disclosed herein, the ti/2 of therapeutic agent is equal to or at less than about: 4 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, or ranges including and/or spanning the aforementioned values. In some embodiments, after a dose of therapeutic agent provided in an embodiment as disclosed herein to a subject, the ti/2 of therapeutic agent (is between about 4 hours and about 6.5 hours or between about 3 hours and about 7 hours. In some embodiments, the ti/2 for a disclosed embodiment is decreased relative to a therapeutic agent alone or an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, the ti/2 of therapeutic agent for a disclosed embodiment is decreased relative to the therapeutic alone or an oil-based comparator vehicle by equal to or at least about: 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, or ranges including and/or spanning the aforementioned values. In some instances, the ti/2 is a fraction of that achieved using a comparator delivery system. In some instances, the time to ti/2 using a disclosed embodiment is 0.5 times, 0.7 times, 0.8 times, 0.9 times, or 0.95 times the ti/2 of a comparator delivery system (or ranges including or spanning the aforementioned values).

[00312] In some embodiments, the lipid-based particle composition comprises nanoparticles having an average size of less than, greater than, or equal to about: 10 nm, 50 nm, 75 nm, 100 nm, 125 nm, 150 nm, 200 nm, 250 nm, 500 nm, 1000 nm, or ranges including and/or spanning the aforementioned values. In some embodiments, the composition comprises nanoparticles having an average size of between about 50 nm and about 150 nm or between about 50 nm and about 250 nm. In some embodiments, the composition comprises nanoparticles having an average size of at least 100 nm. In some embodiments, the size distribution ofthe nanoparticles for at least 50%, 75%, 80%, 90% (or ranges including and/or spanning the aforementioned percentages) of the particles present is equal to, greater than, or less than about: 20 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, or ranges including and/or spanning the aforementioned nm values. In some embodiments, the composition comprises nanoparticles having an average size of less than, greater than, or equal to about: 10 nm, 50 nm, 100 nm, 150 nm, 250 nm, 500 nm, 1000 nm, or ranges including and/or spanning the aforementioned values. In some embodiments, the size distribution of the nanoparticles for at least 90% of the particles present is equal to, greater than, or less than about: 20 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, 750 nm, 1000 nm, 2000 nm, 3000 nm, 4000 nm, 5000 nm, 7500 nm, 10000 nm or ranges including and/or spanning the aforementioned nm values. In some embodiments, the size distribution of the nanoparticles for at least 90% of the particles present is equal to, greater than, or less than about: 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, 750 nm, 1000 nm or ranges including and/or spanning the aforementioned nm values. In some embodiments, the D90 of the particles present is equal to, greater than, or less than about: 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, or ranges including and/or spanning the aforementioned values. In some embodiments, the size distribution of the nanoparticles for at least 70%, 80%, 85%, 90%, 95%, or 99% of the particles present is at least about 100 nm. In some embodiments, the size of the nanoparticle is the diameter of the nanoparticle as measured using any of the techniques as disclosed elsewhere herein and/or known to one of skill in the art. For instance, in some embodiments, the size of the nanoparticle is the measured using dynamic light scattering. In some embodiments, the size of the nanoparticle is the measured using a zeta sizer.

[00313] In some embodiments, the average size of the nanoparticles of a composition as disclosed herein is substantially constant and/or does not change significantly over time (e.g., it is a stable nanoparticle). In some embodiments, after formulation and storage for a period of at least about 1 month (30 days), about 2 months (60 days), about 3 months (90 days), or about 6 months (180 days) (e.g., at ambient conditions, e.g., at 25 °C with 60% relative humidity, or under the other testing conditions disclosed elsewhere herein), the average size of nanoparticles comprising the composition changes less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values.

[00314] In some embodiments, the polydispersity index (PDI) of the nanoparticles of a composition as disclosed herein is less than or equal to about: 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.85, 0.90, or ranges including and/or spanning the aforementioned values. In some embodiments, the size distribution of the nanoparticles is highly monodisperse with a polydispersity index of less than or equal to about: 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 or ranges including and/or spanning the aforementioned values. In some embodiments, the PDI of the nanoparticles of a composition as disclosed herein are between about 0.01 to about 0.80. In some embodiments, the PDI of the nanoparticles of a composition as disclosed herein are between about 0.15 to about 0.25. In some embodiments, the PDI ofthe nanoparticles of a composition as disclosed herein are between about 0.35 to about 0.50.

[00315] In some embodiments, the zeta potential of the nanoparticles of a composition as disclosed herein is less than or equal to about: 1 mV, 3 mV, 4 mV, 5 mV, 6 mV, 7 mV, 8 mV, 10 mV, 20 mV, or ranges including and/or spanning the aforementioned values. In some embodiments, the zeta potential of the nanoparticles is greater than or equal to about: -40 mV, -35 mV, -30 mV, -25 mV, -20 mV, -15 mV, -10 mV, -5 mV, -3 mV, -1 mV, 0 mV, or ranges including and/or spanning the aforementioned values. In some embodiments, the zeta potential and/or diameter of the particles (e.g., measured using dynamic light scattering) is acquired using a zetasizer (e.g., a Malvern ZS90 or similar instrument).

[00316] In some embodiments, the lipid-based particle composition has a pH of less than or equal to about: 2, 3, 4, 5, 6, 6.5, 7, 8, 9, or ranges including and/or spanning the aforementioned values. In some embodiments, the composition has a pH of greater than or equal to about: 2, 3, 4, 5, 6, 6.5, 7, 8, 9, or ranges including and/or spanning the aforementioned values.

[00317] In some embodiments, as disclosed elsewhere herein, the lipid-based particle composition is stable. In some embodiments, for example, after formulation (e.g., in water at concentrations disclosed elsewhere herein) and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), 3 months, or about 6 months, the polydispersity of the nanoparticles changes less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, after formulation (e.g., in water at concentrations disclosed elsewhere herein) and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), 3 months, or about 6 months, the soluble fraction of therapeutic agent in the formulation changes less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, or ranges including and/or spanning the aforementioned values. In some embodiments, after formulation and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), or about 6 months (e.g., at ambient conditions, at 25 °C with 60% relative humidity, or under the other testing conditions disclosed elsewhere herein), the PDI of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, after formulation and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), or about 6 months (e.g., at ambient conditions, at 25 °C with 60% relative humidity, or under the other testing conditions disclosed elsewhere herein), the PDI of nanoparticles comprising the composition changes by less than or equal to about: 0.05, 0.1, 0.2, 0.3, 0.4, or ranges including and/or spanning the aforementioned values. In some embodiments, after formulation and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), or about 6 months (e.g., at ambient conditions, at 25 °C with 60% relative humidity, or under the other testing conditions disclosed elsewhere herein), the average size of nanoparticles comprising the composition changes by less than or equal to about: 10%, 20%, 30%, 40%, 50%, 75%, 100%, 125%, 150%, 175%, 200%, or ranges including and/or spanning the aforementioned values. In some embodiments, after formulation and storage for a period of at least about 1 month, 2 months (e.g., equal to or about 90 days), or about 6 months (e.g., at ambient conditions, at 25 °C with 60% relative humidity, or under the other testing conditions disclosed elsewhere herein), the D90 of nanoparticles comprising the composition changes by less than or equal to about: 10%, 20%, 30%, 40%, 50%, 75%, 100%, or ranges including and/or spanning the aforementioned values.

[00318] In some embodiments, the composition particle size remains consistent (a size change of less than or equal to about: 0%, 0.5%, 1%, 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100% or ranges including and/or spanning the aforementioned values) for a period of at least about 30 days when stored at room temperature, refrigeration, and up to about 37 °C, 38 °C, 39 °C, and/or 40 °C. In some embodiments, the therapeutic agent concentration in the composition remains consistent (a loss of less than or equal to about: 0.5%, 1%, 2%, 3%, 5%, 10%, 20%, 30%, 40%, 50% or ranges including and/or spanning the aforementioned values) for a period of at least about 30 days, 60 days, 90 days, or 120 days when stored at room temperature, refrigeration, and up to about 37 °C, 38 °C, 39 °C, and/or 40 °C. In some embodiments, when stored at room temperature, refrigeration, and up to about 37 °C, 38 °C, 39 °C, and/or 40 °C, the composition is stable (e.g., the particle size or therapeutic agent concentration in the nanoparticles remains consistent and/or has a change of less than or equal to about: 0.5%, 1%, 2%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 100% or ranges including and/or spanning the aforementioned values) for a period of at least about: 2 weeks, 30 days, 2 months, 3 months, 6 months, 9 months, 1 year, or ranges including and/or spanning the aforementioned measures of time.

[00319] In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) of less than about 1, 2, 3, 4, or 5 EBC over about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or greater than 10 days at about 37 °C, 38 °C, 39 °C, and/or 40 °C, with about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% relative humidity. In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) of less than about 4 EBC over at least 5 days at about 40 °C with about 75%, relative humidity. In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) of less than about 2.5 EBC over at least 5 days at about 40 °C with about 75%, relative humidity. In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) of less than about 1 EBC over at least 5 days at about 40 °C with about 75%, relative humidity. In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) that does not significantly differ over at least 5 days at about 40 °C with about 75%, relative humidity. In some embodiments, the composition particle, when added to a second composition (e.g., a beverage), maintains a turbidity (EBC) that does not significantly differ from a control composition (e.g., a beverage) that does not comprise the aqueous composition over at least 5 days at about 40 °C with about 75%, relative humidity.

[00320] In some embodiments, the method of using the lipid-based particle composition and/or of treating a subject with the lipid-based particle composition includes administering to a subject in need of treatment (e.g., orally, topically, etc.) an effective amount of the composition. In some embodiments, the composition (e.g., delivery system) improves the stability of one or more therapeutic agents after ingestion where the composition is exposed to the stomach and/or intestines in an aqueous environment with harsh pH conditions. In some embodiments, the bioavailability of the therapeutic agent (e.g., in the blood of a subject) relative to the initial administered dose is greater than or equal to about: 10%, 20%, 50%, 75%, or ranges including and/or spanning the aforementioned values. In some embodiments, using the disclosed compositions, the oral bioavailability of the therapeutic agent delivered (as measured using AUC) is higher using an embodiment disclosed herein relative to oral delivery of the therapeutic alone. In some embodiments, the oral bioavailability is improved over the therapeutic alone by greater than or equal to about: 10%, 50%, 75%, 100%, 200%, or ranges including and/or spanning the aforementioned values.

[00321] As disclosed elsewhere herein, some embodiments pertain to methods of treating a subject. In some embodiments, the method of treating comprises selecting patient for treatment. In some embodiments, the method of threating comprises administering to the patient an effective amount of a formulation comprising a lipid-based particle composition comprising a therapeutic agent.

[00322] In some embodiments, compositions as described herein may be used to induce at least one effect, e.g. therapeutic effect, that may be associated with at least one therapeutic agent, which is capable of inducing, enhancing, arresting or diminishing at least one effect, by way of treatment or prevention of unwanted conditions or diseases in a subject. As disclosed elsewhere herein, the at least one active agent may be selected amongst therapeutic agents, i.e. agents capable of inducing or modulating a therapeutic effect when administered in a therapeutically effective amount. In some embodiments, the phospholipid(s) by themselves do not induce or modulate a therapeutic effect but endow the composition (e.g., a pharmaceutical composition) with a selected desired characteristic.

[00323] In some embodiments, the compositions disclosed herein can be used in methods of treatment and can be administered to a subject having a condition to be treated. In some embodiments, the subject is treated by administering an effective amount of a composition (e.g., lipid-based particle compositions) as disclosed herein to the subject.

[00324] In some embodiments, the disease or condition to be treated via administration of a composition as disclosed herein may include one or more of liver protection, hangover prevention, vitamin deficiency, alcohol related heart disease, alcohol related neurological conditions, opioid withdraw, attention deficient disorder (ADHD), pain, anxiety, depression, seizures, malaise, nausea, insomnia, work-sleep shift disorder, sleep disturbances, inflammation, immunity, epilepsy, diabetes, cancer (breast, colon, prostate, glioma, etc.), etc. [00325] In some embodiments, the composition is used as a cerebrocirculant, a health supplement, an antiaggregant, an anti-adrenergic at alpha- 1, a sedative, an anticonvulsant, a smooth muscle relaxer, an antitussive, an analgesic, a p-opioid antagonist, a calcium channel blocker, a dopamine mediating anti-locomotive, an antioxidant, an antiaggregant, an antibacterial, an antidiabetic, an antihepatitic, an anti-inflammatory, an anti-leukemic, an antimutagenic, an antiperoxidant, an antiviral, a cancer preventative, an alpha-amylase inhibitor, a 9-hydroxycorynantheidine, an opioid agonist, an analgesic, antidiarrheal, an immunostimulant, an adrenergic, an antimalarial, a vasodilator, an antihypertensive, an muscle relaxer, a diuretic, an antiamnesic, an antipyretic, anti-arrhythmic, antithelmintic, a hypoglycemic, an anti-adrenergic, or combinations of the foregoing.

[00326] In some embodiments, the composition is used to treat a disease or disorder where any one or more of the following is needed: a cerebrocirculant, additional vitamins, an antiaggregant, an anti-adrenergic at alpha-1, a sedative, an anticonvulsant, a smooth muscle relaxer, an antitussive, an analgesic, a p-opioid antagonist, a calcium channel blocker, a dopamine mediating anti-locomotive, an antioxidant, an antiaggregant, an antibacterial, an antidiabetic, an antihepatitic, an anti-inflammatory, an anti-leukemic, an antimutagenic, an antiperoxidant, an antiviral, a cancer preventative, an alpha-amylase inhibitor, a 9- hydroxycorynantheidine, an opioid agonist, an analgesic, antidiarrheal, an immunostimulant, an adrenergic, an antimalarial, a vasodilator, an antihypertensive, an muscle relaxer, a diuretic, an antiamnesic, an antipyretic, anti-arrhythmic, antithelmintic, a hypoglycemic, an anti- adrenergic, or combinations of the foregoing.

[00327] In some embodiments, the lipid-based particle composition is provided for use in treating a condition selected from pain associated disorders (as an analgesic), inflammatory disorders and conditions (as anti-inflammatory), appetite suppression or stimulation (as anoretic or stimulant), vitamin deficiency, symptoms of vomiting and nausea (as antiemetic), intestine and bowl disorders, disorders and conditions associated with anxiety (as anxiolytic), disorders and conditions associated with psychosis (as antipsychotic), disorders and conditions associated with seizures and/or convulsions (as antiepileptic or antispasmodic), sleep disorders and conditions (as anti-insomniac), disorders and conditions which require treatment by immunosuppression, disorders and conditions associated with elevated blood glucose levels (as antidiabetic), disorders and conditions associated with nerve system degradation (as neuroprotectant), inflammatory skin disorders and conditions (such as psoriasis), disorders and conditions associated with artery blockage (as anti-ischemic), disorders and conditions associated with bacterial infections, disorders and conditions associated with fungal infections, proliferative disorders and conditions, disorders and conditions associated with inhibited bone growth, post trauma disorders, and others.

[00328] In some embodiments, the lipid-based particle composition is provided for use in a method of treating a subject suffering from a condition selected from pain associated disorders, inflammatory disorders and conditions, symptoms of vomiting and nausea, intestine and bowl disorders, disorders and conditions associated with anxiety, disorders and conditions associated with vitamin deficiency, disorders and conditions associated with psychosis, disorders and conditions associated with seizures and/or convulsions, sleep disorders and conditions, disorders and conditions which require treatment by immunosuppression, disorders and conditions associated with elevated blood glucose levels, disorders and conditions associated with nerve system degradation, inflammatory skin disorders and conditions, disorders and conditions associated with artery blockage, disorders and conditions associated with bacterial infections, disorders and conditions associated with fungal infections, proliferative disorders and conditions, and disorders and conditions associated with inhibited bone growth, post trauma disorders and others, a patient in need of appetite suppression or stimulation. In some embodiments, the method comprises administering to the subject an effective amount of a composition of this disclosure. [00329] In some embodiments, the lipid-based particle compositions (described herein may be used for inducing, enhancing, arresting or diminishing at least one effect, by way of treatment or prevention of unwanted conditions or diseases in a subject. The therapeutic agent (substance, molecule, element, compound, entity, or a combination thereof) may be selected amongst therapeutic agents, i.e. agents capable of inducing or modulating a therapeutic effect when administered in a therapeutically effective amount, and non- therapeutic agents, i.e. which by themselves do not induce or modulate a therapeutic effect but which may endow the pharmaceutical composition with a selected desired characteristic.

[00330] In some embodiments, a lipid-based particle compositions as disclosed herein may be selected to treat, prevent or ameliorate any pathology or condition. In some embodiments, administering of a therapeutic amount of the composition or system described herein, whether in a concentrate form or in a diluted formulation form, is effective to ameliorate undesired symptoms associated with a disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease from occurring or a combination of two or more of the above.

[00331] Surprisingly and advantageously, some embodiments disclosed herein do not require one or more ingredients typically used to prepare liposomes and/or nanoparticle formulations. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of one or more of lipids (other than phospholipids), triglycerides, sterols, lecithin surfactants, hyaluronic acid, Alcolec S, Alcolec BS, Alcolec XTRA-A, polysorbates (such as Polysorbate 80 and Polysorbate 20), monoglycerides, diglycerides, glyceryl oleate, poloxamers, terpenes, sodium alginate, polyvinylpyrrolidone, L-alginate, chondroitin, poly gamma glutamic acid, gelatin, chitosan, com starch, polyoxyl 40-hydroxy castor oil, Tween 20, Span 80, or the salts of any of thereof. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of a surfactant and/or emulsifiers other than a phospholipid. In some embodiments, the lipid-based particle compositions disclosed herein lack an emulsifier at concentrations greater than about 1/10^th that of a phospholipid. In some embodiments, the lipid-based particle compositions disclosed herein lack an emulsifier at concentrations greater than about l/10^th that of a phosphatidylcholine. In some embodiments, the lipid-based particle compositions lack unhydrogenated phospholipids. In some embodiments, the lipid-based particle compositions lack hydrogenated phospholipids. In some embodiments, the lipid-based particle compositions comprise one or more unhydrogenated or hydrogenated phospholipids. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, and/or less than about 0.5% of one or more of a buffering agent, a polymeric stabilizing agent, and/or sodium hydroxide.

[00332] In some embodiments, the lipid-based particle compositions disclosed herein lack nonnatural ingredients. In some embodiments, the lipid-based particle compositions disclosed are synthetic and not found in nature.

[00333] In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of one or more organic bases (which may include, but are not limited to: butyl hydroxyl anisole (BHA), butyl hydroxyl toluene (BHT) and sodium ascorbate). In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of whey protein isolate. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of ticamulsion 3020, purity gum, gum Arabic, and/or a modified gum Arabic. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none one or more of fatty acids, triglycerides triacylglycerols, acylglycerols, fats, waxes, sphingolipids, glycerides, sterides, cerides, glycolipids, sulfolipids, lipoproteins, chylomicrons and the derivatives of these lipids. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of a surfactant. In some embodiments, the lipid-based particle compositions disclosed herein lack, contain less than about 2%, less than about 0.5%, and/or substantially none of one or more of polyglycolized glycerides and polyoxyethylene glycerides of medium to long chain mono-, di-, and triglycerides, such as: almond oil PEG-6 esters, almond oil PEG-60 esters, apricot kernel oil PEG-6 esters (Labrafd® M1944CS), caprylic/capric triglycerides PEG-4 esters (Labrafac® Hydro WL 1219), caprylic/capric triglycerides PEG-4 complex (Labrafac® Hydrophile), caprylic/capric glycerides PEG-6 esters (Softigen® 767), caprylic/capric glycerides PEG-8 esters (Labrasol®), castor oil PEG-50 esters, hydrogenated castor oil PEG-5 esters, hydrogenated castor oil PEG-7 esters, 9 hydrogenated castor oil PEG-9 esters, com oil PEG-6 esters (Labrafd® M 2125 CS), com oil PEG-8 esters (Labrafd® WL 2609 BS), com glycerides PEG-60 esters, olive oil PEG-6 esters (Labrafd® Ml 980 CS), hydrogenated palm/palm kernel oil PEG-6 esters (Labrafil® M 2130 BS), hydrogenated palm/palm kernel oil PEG-6 esters with palm kernel oil, PEG-6, palm oil (Labrafil® M 2130 CS), palm kernel oil PEG-40 esters, peanut oil PEG-6 esters (Labrafil® M 1969 CS), glyceryl laurate/PEG-32 laurate (Gelucire® 44/14), glyceryl laurate glyccry I/PEG 20 laurate, glyceryl laurate glyceryl/PEG 32 laurate, glyceryl, laurate glyceryl/PEG 40 laurate, glyceryl oleate/PEG-20 glyceryl, glyceryl oleate/PEG-30 oleate, glyceryl palmitostearate/PEG-32 palmitostearate (Gelucire® 50/13), glyceryl stearate/PEG stearate, glyceryl stearate/PEG-32 stearate (Gelucire® 53/10), saturated polyglycolized glycerides (Gelucire® 37/02 and Gelucire® 50/02), triisostearin PEG-6 esters (i.e. Labrafd® Isostearique), triolein PEG-6 esters, trioleate PEG-25 esters, polyoxyl 35 castor oil (Cremophor® EL or Kolliphor® EL), polyoxyl 40 hydrogenated castor oil (Cremophor® RH 40 or Kolliphor® REMO), polyoxyl 60 hydrogenated castor oil (Cremophor® RH60), polyglycolized derivatives and polyoxyethylene esters or ethers derivatives of medium to long chain fatty acids, propylene glycol esters of medium to long chain fatty acids, which can be used including caprylate/caprate diglycerides, glyceryl monooleate, glyceryl ricinoleate, glyceryl laurate, glyceryl dilaurate, glyceryl dioleate, glyceryl mono/dioleate, polyglyceryl- 10 trioleate, poly glyceryl- 10 laurate, polyglyceryl- 10 oleate, and poly glyceryl- 10 mono dioleate, propylene glycol caprylate/caprate (Labrafac® PC), propylene glycol dicaprylate/dicaprate (Miglyol® 840), propylene glycol monolaurate, propylene glycol ricinoleate, propylene glycol monooleate, propylene glycol dicaprylate/dicaprate, propylene glycol dioctanoate, sucrose esters surfactants such as sucrose stearate, sucrose distearate, sucrose palmitate, sucrose oleate, and combinations thereof.

[00334] Some embodiments also encompass methods for making and/or administering the disclosed compositions. Multiple techniques of administering the lipid-based particle compositions as disclosed herein exist including, but not limited to, oral, rectal, topical, aerosol, injection and parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, intrathecal, direct intraventricular, intraperitoneal, intranasal and intraocular injections. In some embodiments, administration is performed through oral pathways, which administration includes administration in an emulsion, aqueous solution, capsule, tablet, fdm, chewing gum, suppository, granule, pellet, spray, syrup, or other such forms. As further examples of such modes of administration and as further disclosure of modes of administration, disclosed herein are various methods for administration of the disclosed compositions including modes of administration through intraocular, intranasal, and intra auricular pathways. [00335] In some embodiments, where a topical is provided, topical permeation enhancers may be included and may be selected from, but not inclusive of, the following: dimethyl sulfoxide, dimethyl sulfone, ethanol, propylene glycol, dimethyl isosorbide, polyvinyl alcohol, CapryolTM 90, Labrafd Ml 944 CS, Labrasol, Labrasol ALF, LauroglycolT M90, Transcutol HP, Capmul S12L, Campul PG-23 EP/NF, Campul PG-8 NF. The topical may include one or more of Lipoid’s Skin Lipid Matrix 2026 technology, lipid/oil based ingredients or oil soluble ingredients, and includes Captex 170 EP as a skin permeation enhancer, argan oil, menthol, arnica oil, camphor, grapefruit seed oil, For example, dimethyl sulfoxide, dimethyl isosorbide, topical analgesics such as lidocaine, wintergreen oil, and terpenes such as guaiacol. In some embodiments, any one or more of these ingredients is present in the topical composition at a dry wt. % of equal to or less than about: 0.1%, 0.5%, 1%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values. In some embodiments, any one or more of these ingredients is present in the topical at a wet wt % of equal to or at least about: 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, or ranges including and/or spanning the aforementioned values.

[00336] In some embodiments, the lipid-based particle compositions disclosed herein can be in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose, or the like, and can contain auxiliary substances such as wetting or emulsifying agents, pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, colors, and the like, depending upon the route of administration and the preparation desired. See, e.g., “Remington: The Science and Practice of Pharmacy”, Lippincott Williams & Wilkins; 20th edition (June 1, 2003) and “Remington’s Pharmaceutical Sciences,” Mack Pub. Co.; 18^th and 19^th editions (December 1985, and June 1990, respectively). In some embodiments, these additional agents are not added. Such preparations can include liposomes, microemulsions, micelles, and/or unilamellar or multilamellar vesicles.

[00337] In some embodiments the lipid-based particle suspension solution disclosed herein have improved shelf life as indicated in part by the ability of the lipid-based particle composition to remain suspended in the liquid broth without aggregating or separating/settling from solution. For example, in some embodiments, the lipid-based particle suspension solution disclosed remain solubilized for a period greater than or equal to 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 24 months, or ranges including and/or spanning the aforementioned values. In some embodiments, the shelf life can be determined as the period of time in which there is 95% confidence that at least 50% of the response (therapeutic agent(s) concentration or particle size) is within the specification limit. This refers to a 95% confidence interval and when linear regression predicts that at least 50% of the response is within the set specification limit.

[00338] In some embodiments, the shelf life can be determined as a time where the concentration of the active ingredient has changed (e.g., lessened) by less than or equal to 30%, 25%, 20%, 15%, 10%, 5%, 2.5%, or ranges including and or spanning the aforementioned ranges.

[00339] In some embodiments, the compositions disclosed herein, when provided in a lipid- based particle suspension solution, have improved thermal stability.

[00340] In some embodiments, thermal sterilization includes exposing and/or heating a composition to a temperature of equal to or at least about 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, 90 °C, 100 °C, 110 °C, 120 °C, 130 °C, 140 °C, 150 °C, or 160 °C. In some embodiments, the thermal sterilization is performed for a time period of equal to or at least about: 1 second, 2 seconds, 3 seconds, 4 seconds, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, 30 seconds, 45 seconds, 1 minute, 2 minutes, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes, or ranges including and/or spanning the aforementioned values.

[00341] In some embodiments, after a 15 or 30 day period, the particle size and/or PDI varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40 %, 50%, 75%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, or ranges including and/or spanning the aforementioned values. In some embodiments, using the lipid-based particle compositions disclosed herein, after a storage period of equal to or at least about 15 days, 30 days, 45 days, 60 days, 6 months, 12 months, 18 months, or 24 month periods, the concentration of the therapeutic agent in the aqueous product (e.g., a beverage, carbonated or not, alcoholic or not) drops by less than or equal to about: 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2.0%, 2.5%, 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, or ranges including and/or spanning the aforementioned values. In some embodiments, the storage conditions include temperatures of equal to or at least about: 2 °C, 4 °C, 6 °C, 8 °C, 10 °C, 20 °C, 40 °C, 60 °C, or ranges including and/or spanning the aforementioned values.

[00342] In some embodiments, the compositions disclosed herein, when provided in a lipid- based particle suspension solution, are stable during ozonation sterilization, UV sterilization, heat sterilization (e.g., pasteurization), filtration sterilization, and/or gamma irradiation during beverage preparation and packaging. In some embodiments, the particle size and/or PDI after sterilization (e.g., exposure to techniques that allow sterilization of the composition) varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 75%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, or ranges including and/or spanning the aforementioned values. In some embodiments, the therapeutic agent concentration after sterilization (e.g., exposure to techniques that allow sterilization of the composition) drops by less than or equal to about: 0.05%, 0.1%, 0.5%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, or ranges including and/or spanning the aforementioned values. In some embodiments, after sterilization, the lipid-based particle suspension solutions comprising lipid-based particle compositions have a shelf life of equal to or greater than 6 months, 12 months, 14 months, 16 months, 18 months, 19 months, 24 months, or ranges including and/or spanning the aforementioned values (e.g., a standard storage conditions).

[00343] Dry powder formulations or liquid embodiments may also be used in a variety of consumer products. For example, in some embodiments, dry powders can be added (e.g., scooped, from a packet, squirted from a dispenser, etc.) into any consumer product.

[00344] In some embodiments, liquid solutions or powdered lipid particle formulations can be coated onto and/or added into a consumer product (e.g., sprayed and/or squirted from a dispenser, through dipping, soaking, rolling, dusting, etc.). In some embodiments, the consumer product is a food product (e.g., beverages, candies, lollipops, edibles, food, ingestible, buccal adhesives, etc.).

[00345] In some embodiments, the lipid particles supplement and/or fortify a consumer product with a therapeutic agent from the lipid particles. In some embodiments, the therapeutic agent is delivered to the user in a greater quantity than would be achieved using (e.g., consuming) the therapeutic agent alone.

[00346] In some embodiments, coating is performed with an aqueous or solvent solution of the lipid particles. For example, the solution may be sprayed (e.g., via a spray nozzle, atomizer, etc.) or otherwise coated (e.g., dip-coated, etc.) onto a consumer product. In some embodiments, pharmaceutical coating equipment (e.g., that used to coat tablets, beads, drug layered/coated films) is used to coat a consumer product. In some embodiments, fluid bed technology, film bed technology, dry powder laying technology, and/or combinations thereof are used to coat a consumer product. In some embodiments, film coating is used to coat a consumer product.

[00347] In some embodiments, prior to coating with a liquid solution of lipid particles, the consumer product is dried completely. Then, after coating, the fortified consumer product is dried. In other implementations, a consumer product is solution coated (e.g., prior to drying). After coating and/or spraying with the lipid particles, the consumer product can then be dried together with the lipid particles to provide a fortified consumer product. In some embodiments, as disclosed elsewhere herein, a powder can be used to coat a consumer product. [00348] In some embodiments, the lipid-based particle composition as disclosed herein may be added, injected, measured, and/or poured into a beverage. In some embodiments, the lipid- based particle composition is added to a beverage as a dry solid or as a concentrated solution lipid particle solution (e.g., an aqueous composition as provided elsewhere herein).

[00349] In some embodiments, to prepare a consumer product, a lipid-based particle composition is provided to the consumer product (e.g., a beverage, a topical ointment, etc.) at a concentration that is equal to or at least about: 10 pg/mL (or “mcg/mL”), 50 pg/mL. 100 pg/mL, 150 pg/mL, 200 pg/mL, 250 pg/mL, 350 pg/mL, 450 pg/mL, 500 pg/mL, 750 pg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 1.80 mg/mL, 2.0 mg/mL, 2.25 mg/mL, 2.5 mg/mL, 2.6 mg/mL, 3.0 mg/mL, 4.0 mg/mL, 5.0 mg/mL, or ranges including and/or spanning the aforementioned values. In some embodiments, enough of the lipid-based particle composition is added to afford a total concentration of active ingredient in the consumer product of equal to or at least about: 1 pg/mL (or “mcg/mL”), 5 pg/mL, 10 pg/mL, 15 pg/mL, 20 pg/mL, 25 pg/mL, 35 pg/mL, 45 pg/mL, 50 pg/mL, 75 pg/mL, 100 pg/mL, 125 pg/mL, 150 pg/mL, 175 pg/mL, 180 pg/mL, 200 pg/mL, 225 pg/mL, 250 pg/mL, 500 pg/mL, or ranges including and/or spanning the aforementioned values.

[00350] In some embodiments, where a concentrated lipid-based particle composition in aqueous solution is added to the consumer product, to each milliliter of the consumer product is added equal to or at least about: 0. 1 pL, 0.25 pL, 0.5 pL, 0.75 pL, 1 pL, 2.5 pL, 5.0 pL, 7.5 pL, 10 pL, 25 pL, 50 pL, 75 pL, 100 pL, 250 pL, or 500 pL of the concentrated lipid-based particle solution (or ranges including and/or spanning the aforementioned values).

[00351] Several illustrative embodiments of compositions and methods have been disclosed. Although this disclosure has been described in terms of certain illustrative embodiments and uses, other embodiments and other uses, including embodiments and uses which do not provide all the features and advantages set forth herein, are also within the scope of this disclosure. Components, elements, features, acts, or steps can be arranged or performed differently than described and components, elements, features, acts, or steps can be combined, merged, added, or left out in various embodiments. All possible combinations and subcombinations of elements and components described herein are intended to be included in this disclosure. No single feature or group of features is necessary or indispensable.

[00352] Certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation also can be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations, one or more features from a claimed combination can in some cases be excised from the combination, and the combination may be claimed as a subcombination or variation of a subcombination. [00353] Any portion of any of the steps, processes, structures, and/or devices disclosed or illustrated in one embodiment, flowchart, or example in this disclosure can be combined or used with (or instead of) any other portion of any of the steps, processes, structures, and/or devices disclosed or illustrated in a different embodiment, flowchart, or example. The embodiments and examples described herein are not intended to be discrete and separate from each other. Combinations, variations, and other implementations of the disclosed features are within the scope of this disclosure.

[00354] Further, while illustrative embodiments have been described, any embodiments having equivalent elements, modifications, omissions, and/or combinations are also within the scope of this disclosure. Moreover, although certain aspects, advantages, and novel features are described herein, not necessarily all such advantages may be achieved in accordance with any particular embodiment. For example, some embodiments within the scope of this disclosure achieve one advantage, or a group of advantages, as taught herein without necessarily achieving other advantages taught or suggested herein. Further, some embodiments may achieve different advantages than those taught or suggested herein.

[00355] The section headings used herein are for organizational purposes only and are not to be construed as limiting the described subject matter in any way. All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose. When definitions of terms in incorporated references appear to differ from the definitions provided in the present teachings, the definition provided in the present teachings shall control. It will be appreciated that there is an implied “about” prior to the temperatures, concentrations, times, etc. discussed in the present teachings, such that slight and insubstantial deviations are within the scope of the present teachings herein. In this application, the use of the singular includes the plural unless specifically stated otherwise.

EXAMPLES

[00356] The following examples are included to demonstrate preferred embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the disclosure, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure.

I. Example 1: Preparation of Embodiments of the Composition

[00357] Unless otherwise noted, the ingredients used herein were obtained from the following vendors: Sunflower derived phosphatidylcholine was purchased from American Lecithin Company (a Lipoid Company listed as “MCT”), potassium sorbate was purchased from Spectrum Chemicals, deionized water was purchased from Walmart, and sodium benzoate was purchased from Spectrum Chemicals. The phosphatidylcholine was a mixture of H 20 grade including over 20 % phosphatidylcholine and H 90 grade including over 90 % phosphatidylcholine .

[00358] Particle size and zeta potential of liquid was measured on a Malvern ZS90 Zetasizer (Malvern, UK). Products were measured in low-volume, disposable cuvettes and zeta cassettes. Active agent concentrations, related substances and identity (retention time) were measure by high-pressure liquid chromatography (HPLC) at 374 Labs (Reno, NV). Residual solvents were measured by gas chromatography (GC), and heavy metals by inductive coupled plasma-optical emission spectrometry (ICP-OES) at 374 Labs. Rapid preservative effectiveness testing can be determined by a reduction in colony forming units (CFU) of test microorganisms at Microchem Laboratory (Round Rock, Texas). Preservative effectiveness testing can confirmed that the compositions were resistant to bacterial growth (by measuring colony forming units (CFUs) per volume in a given amount of time.

[00359] Manufacturing Process: Formulations containing active agents and varying amounts of plant extract were prepared using a solvent-free manufacturing process, as shown in Tables 4 to 9. To prepare the composition, water was heated to 75 °C before adding additional ingredients. Sodium bicarbonate was added to adjust the pH. The required amounts of plant extract were dispersed in the aqueous solution at varying concentrations as well as other hydrophilic components. Afterwards, the lipophilic components were added with high shear mixing. The active ingredient was then added to achieve a final concentration of 15 mg/mL. Once high shear mixing was completed, the mixture was high pressure homogenized until a homogeneous mixture was produced. [00360] All water-soluble formulation ingredients were dissolved into deionized water at the specified concentrations. Aqueous solutions were heated and filtered prior to further use. An appropriate amount of aqueous solution was transferred to the glass vessel containing the dried lipid ingredients. The glass vessel was transferred to a heating mantel and warmed with constant stirring from an overhead mixer. Mixing was continued until a homogenous slurry of lipids in water was formed. The full volume of lipid slurry was processed through a microfluidizer (Microfluidics Corporation) 0 to 10 times at a processing pressure of 10,000 - 30,000 PSI. Alternatively, the volume of lipid slurry can be processed at a pressure of 10,000 - 30,000 PSI such that the material is recirculated back into the unprocessed volume for a period of time until the desired particle size characteristics are achieved. The resulting lipid nanoparticle solution was cooled with continuous stirring for 12 - 24 hours before characterizing and fill-finish.

Table 4 - Exemplary aqueous formula

Table 5 - Exemplary aqueous formula

Table 6 - Exemplary aqueous formula

Table 7 - Exemplary aqueous formula

Table 8 - Exemplary aqueous formula

Table 9 - Exemplary dried formula

II. Example 2: Preparation of Nanoparticles and Stability Study

[00361] Multiple nanoparticles were prepared using the manufacturing process described in Example 1. 250 gram batches containing the concentrations of components described in Table 25, Table 26, and Table 27 below were prepared and 30 grams were fdled into 30 mb dropper cap bottles for stability testing. Samples were stored at controlled 2 - 8°C, room temperature (25°C/60% relative humidity), or accelerated conditions (40°C/75% relative humidity or 55 °C) for testing. Shown in Table 28 are changes in concentration of the active agent, changes in Z- average particle size, changes in Polydispersity Index (PDI), and changes in phase separation ratio over the period of time tested for each storage condition. Forced hazing tests of some of the formulations were conducted by adding a standardized amount of encapsulated active ingredient to a beaker. To the beaker, a standardized amount of room temperature liquid (e.g, beer) was added to the beaker. Stirring by magnetic stir bar was initiated at 500 RPM and maintained for 2 minutes. Afterwards, material was transferred to a turbidity sample cell. After a TO turbidity measurement was taken, the sample was stored in the turbidity sample cell at 40°C/75% RH for 5 days. Turbidity readings were taken daily (not including weekends or holidays) during this time. Studies were performed such that neither the first nor fifth day of the study fell on a weekend. Table 28 contains particle size and potency data for various formulation enabling examples. For formulations at storage temperatures of 25 C and 40 C, Tl, T2, T3, and T4 are 1 month, 2 months, 3 months, and 6 months respectively. For formulations at storage temperatures of 55 C, Tl, T2, T3, and T4 are 1 week, 2 weeks, 3 weeks, and 4 weeks respectively.

[00362] Storage at 40°C/75% is generally understood to increase degradation kinetics by a factor of 4 compared to controlled room temperature based on the Arrhenius equation.

[00363] It was found that the addition of plant extracts had the impact of reducing the foam decay rate in formulations dispersed in carbonated beverages such as beer. Foam decay rate was measured by the graduated cylinder method. Briefly, the method was performed by first dispersing the nanoparticle formulation in beer and then pouring 100 mb of the nanoparticle in cold beer into a 500 mb graduated cylinder. The maximum level of foam in the cylinder was noted, and then the decay of the foam down the walls of the cylinder was filmed. The level of foam in the graduated cylinder (measured in mb) was charted at various timepoints, and the resulting data was processed for curve fitting according to exponential decay by the following formula: Y = Yf + (Yi-Yf)*exp(-k*t), where Y is the foam level measured, Yf is the final foam level, Yi is the initial foam level, k is the foam decay rate in units of per second ( 1/s), and t is time in seconds. For example, a control of beer with no additives present was found to exhibit a foam decay rate of 0.0061/s. A formulation of encapsulated xanthohumol without added plant extract dispersed in beer was found to exhibit a foam decay rate of 0.0105/s, which is significantly higher compared with the control. In contrast, a formulation prepared of the same xanthohumol composition but with the addition of plant extract at a concentration of 1.0 w/w% in the nanoparticle formulation when dispersed in beer was found to exhibit a foam decay rate of 0.0049/s. Therefore, the inclusion of 1.0 w/w% plant extract in the formulation was able to reduce the foam decay rate by more than a factor of 2 compared to a formulation without plant extract. Foam decay rate was also decreased in comparison to a control with no xanthohumol formulation present. See Table 29 for foam decay data for the xanthohumol formulation in beer with added plant extract and Table 30 for foam decay data for the xanthohumol formulation in beer without added plant extract. See Table 31 for foam decay data for a beer control with no xanthohumol formulation added.

[00364] It is proposed that the saponin content of the plant extract used is largely responsible for this change in foaming characteristics. In the foam decay rate experiment previously mentioned, the plant extract used was ~98 w/w% saponins. Saponins are natural surfactant compounds, and the presence of surfactants is well known to increase the presence and strength of foam in many applications including beer. Foam decay rate and other foam -related attributes are considered key product quality attributes to many products including beer. Technology which allows for this product quality attribute to be modified are therefore concluded to be quite valuable. Depending on the application, a lower foam decay rate is desirable compared to a higher foam decay rate. Experiments have demonstrated that a xanthohumol formulation in the absence of plant extracts bearing significant concentrations of saponins contribute an increased foam decay rate in beer applications compared to a control of beer with no xanthohumol added. The presence of plant extracts bearing significant saponin concentrations has the impact of reducing the foam decay rate likely due to the surfactant properties of the saponins used. In many applications, this reduced foam decay rate provides a significant improvement in product quality.

[00365] It was found that increases in the concentration of the phosphatidylcholine or plant extract lowers the viscosity of the formulations. In addition, it was found that, for samples that were dispersed in beer, the presence of the plant extract has the effect of reducing the turbidity of the beer containing the formulation. Also, formulations that are higher in phosphatidylcholine (more H90 than H20) or had less total lipid also showed lower turbidity when dispersed in beer.

[00366] It is proposed that the reduction in viscosity of formulations caused by plant extract presence is due to the saponin content of the plant extract. In the cases presented here, plant extract saponin content was significant in all of them. Saponins are surfactant compounds, and surfactants have been demonstrated to reduce viscosity in many applications, including with emulsions. However, there are also many cases in which the presence of surfactants have been demonstrated to increase viscosity as well. The exact mechanism whereby the plant extracts which have significant saponin content cause a reduction in formulation viscosity is unknown, but it is expected to result from modification of intermolecular forces caused by the surfactant properties of the saponins of the plant extract

III. Example 3: Preparation and Stability of Encapsulated Xanthohumol Liquid Concentrates

[00367] Numerous formulations comprising varying amounts of xanthohumol and phosphatidylcholine were produced. Each formulation differed slightly with respect to lipid composition and ratio of xanthohumol to phosphatidylcholine. Reported here are 6 exemplary formulations. As utilized in the below Tables 10 to 22, “RH” stands for relative humidity, while “UC” stands for uncontrolled.

[00368] The data showed that the provided formulations maintained chemical stability for at least 30, 60, 90, and/or 180 days at 25 °C with 60% relative humidity.

[00369] The data showed that the provided formulations maintained chemical stability for at least 30, 60, and/or 90 days at 40 °C with 75% relative humidity.

[00370] The data showed that the provided formulations maintained stability (particle size) for at least 30, 60, 90, and/or 180 days at 25 °C with 60% relative humidity.

[00371] The data showed that the provided formulations maintained stability (particle size) for at least 30, 60, 90, and/or 180 days at 40 °C with 75% relative humidity.

[00372] The data showed that the provided formulations maintained stability (PDI) for at least 30, 60, 90, and/or 180 days at 25 °C with 60% relative humidity.

[00373] The data showed that the provided formulations maintained stability (PDI) for at least 30, 60, 90, and/or 180 at 40 °C with 75% relative humidity.

Table 10 - Chemical stability of formulation 6 liquid concentrate (see FIGs. 3A-3B)

Table 11 - Chemical stability of Formulations 7-11 as liquid concentrates at 25 °C with 60% relative humidity (see FIGs. 3C-3L)

Table 12 - Chemical stability of Formulations 7-11 as liquid concentrates at 40 °C with 75% relative humidity (see FIGs. 3C-3L)

Table 13 - Stability (Z -Average Particle Size) of Formulations 7-11 as liquid concentrates at 25 °C with 60% relative humidity (see FIGs. 4A-4J)

Table 14 - Stability (PDI) of Formulations 7-11 as liquid concentrates at 25 °C with 60% relative humidity (see FIGs. 4A-4J)

Table 15 - Stability (Z -Average Particle Size) of Formulations 7-11 as liquid concentrates at 40 °C with 75% relative humidity (see FIGs. 4A-4J)

Table 16 - Stability (PDI) of Formulations 7-11 as liquid concentrates at 40 °C with 75% relative humidity (see FIGs. 4A-4J)

Table 17 - Formulation 6 liquid concentrate comprised:

Table 18 - Formulation 7 liquid concentrate comprised:

Table 19 - Formulation 8 liquid concentrate comprised:

Table 20 - Formulation 9 liquid concentrate comprised:

Table 21 - Formulation 10 liquid concentrate comprised:

IV. Example 4: Preparation and Stability of Encapsulated Xanthohumol in Beverages

[00374] Three formulations comprising varying amounts of xanthohumol and phosphatidylcholine were produced. Each formulation differed slightly with respect to lipid composition and ratio of xanthohumol to phosphatidylcholine.

[00375] Formulations and beverages comprising the formulations were characterized, including Particle size (PSD), polydispersity index (PDI), zeta potential (ZP), and active concentration. PSD, PDI, and ZP was measured using batch mode dynamic light scattering (DLS) and electrophoretic mobility. Therapeutic Ingredients, such as the active ingredient Vitamin D3 (Cholecalciferol) was measured using a qualified UPLC-MS/MS method.

[00376] The stability of each formulation was determined by measuring turbidity in alcoholic and non-alcoholic beverages daily for five consecutive days when stored at 38 °C and 75% relative humidity (RH). Briefly, the turbidity of beer containing various target concentrations of encapsulated vitamin D3 and encapsulated xanthohumol was monitored at pre-defined time points using a HACH 2100N turbidimeter following ISO method 7027.

[00377] Formulations comprising varying amounts of vitamin D3 were produced. Formulations comprising varying amounts of xanthohumol were produced. Each formulation differed slightly with respect to lipid composition and ratio of vitamin D3 to lipid or xanthohumol to lipid. As shown in FIG. 1, formulations were solubilized in a non-alcoholic lager at either 0.019 mg D3 and 5 mg xanthohumol per 330 mL serving (thin red line and thin blue line), or 0.125 mg D3 and 15 mg xanthohumol per 330 mL serving (thick red line and thick blue line) and stored at 40 °C / 75% RH for 5 days. Turbidity measurements were taken on each day. As a control, a non-alcoholic lager with no vitamin D3 or xanthohumol was stored under the same conditions and measured daily. The turbidity of the non-alcoholic lagers did not vary significantly over the 5 days. Indicating the encapsulated vitamin D3 formulations and encapsulated xanthohumol formulations did not negatively impact the stability of the nonalcoholic lager. These results showed that vitamin D3 encapsulated or xanthohumol encapsulated formulations described herein remained stable under accelerated conditions for at least 5 days when introduced to non-alcoholic beverages (e.g., lagers).

[00378] As shown in FIG. 2A, xanthohumol encapsulated in H90 phosphatidylcholine was solubilized in an alcoholic lager at either 5 mg per 330 mb serving, or 15 mg per 330 mb serving and stored at 38 °C / 75% RH for 5 days. Turbidity measurements were taken on days 1, 3, and 5 (reported as NTU). As a control, the alcoholic lager with no xanthohumol was stored under the same conditions and measured on days 1, 3, and 5. The turbidity of the alcoholic lager with xanthohumol did not significantly change over 5 days of storage.

[00379] As shown in FIG. 2B, xanthohumol encapsulated in 85G phosphatidylcholine was solubilized in a non-alcoholic lager at either 5 mg per 330 mb serving, or 15 mg per 330 mb serving and stored at 38 °C / 75% RH for 5 days. Turbidity measurements were taken on days 1, 3, and 5 (reported as NTU). As a control, the non-alcoholic lager with no xanthohumol was stored under the same conditions and measured on days 1, 3, and 5. The turbidity of the nonalcoholic lager with xanthohumol did not significantly change over 5 days of storage.

[00380] As shown in FIG. 2C, xanthohumol encapsulated in H90 phosphatidylcholine was solubilized in a non-alcoholic lager at either 5 mg per 330 mb serving, or 15 mg per 330 mb serving and stored at 38 °C / 75% RH for 5 days. Turbidity measurements were taken on days 1, 3, and 5 (reported as NTU). As a control, the non-alcoholic lager with no xanthohumol was stored under the same conditions and measured on days 1, 3, and 5. The turbidity of each of the non-alcoholic lagers with xanthohumol and the control non-alcoholic lager without xanthohumol increased by day 5 of storage.

[00381] As shown in FIGs. 4A-4J, formulation 6 liquid concentrate comprising xanthohumol was added to various beers and the chemical stability of xanthohumol was measured over time. The beer formulations were stored at either 4 °C with uncontrolled relative humidity, or under accelerated aging conditions of 40 °C with 75% relative humidity. The results showed that xanthohumol provided in formulations described herein was chemically stable for at least 90 days in beer when stored at 4 °C. See Table 23 and Table 24.

Table 23 - Chemical stability of xanthohumol comprising Formulation 6 liquid concentrate over time in various beers at 4 °C with uncontrolled humidity.

Table 24 - Chemical stability of xanthohumol comprising Formulation 6 liquid concentrate over time in various beers at 40 °C with 75% relative humidity.

V. Example 5: Method of Treating a Condition

[00382] Based on the inventor’s experience, the following prophetic results are projected using controlled studies.

[00383] At least three groups of female and male patients are admitted to treatment after having had been diagnosed with a condition, or are at risk of a condition, or are in need of treatment for a condition. Non-limiting conditions and therapeutic ingredients for such conditions may include dihydromyrciten for liver protection, dihydromyrciten for hangover prevention, vitamins for vitamin deficiency, CoQlO and/or omega 3 fatty acids for alcohol related heart disease, and/or phosphatidylserine, huperzine A, and/or Bacopa monnieri extract for alcohol related neurological conditions. A first group is treated orally with a therapeutic containing lipid-based particle composition in a beverage as disclosed herein and on a schedule, such as a daily schedule. A second group is treated with the therapeutic ingredient not contained in a lipid-based particle in a similar beverage orally and on the same schedule. A third group is treated with a placebo in a similar beverage orally and on the same schedule. Group one of patients experience an improvement in the condition or symptoms of the condition. The results show statistically significant improvements in group one relative to either groups two or three.

VI. Example 6: Method of Testing Encapsulated Ingredient Stability in an Alcoholic or non-Alcoholic Drink

[00384] Encapsulated ingredients are introduced to an alcoholic or non-alcoholic drink at one or more concentrations. The finished product containing the encapsulated ingredient can be mixed until the product is homogenous. The finished product can be divided into individual vials, capped, and placed at the recommended storage condition, such as at 2 - 8 °C, for a period of time, such as 6 months. At predetermined time points, the product can be removed from storage and assessed for visual appearance, microbiology, concentration of ingredient remaining (percent remaining), formation of substances from degradation of the ingredient (e.g., such as isoxanthohumol), turbidity of the alcoholic or non-alcoholic drink, and size of the encapsulated ingredient, such as nanoparticle size.

[00385] Microbiology can be tested to determine the amount of living microbes in the finish product by spectroscopy, plating (e.g. agar plates), live/dead staining, etc. The concentration of ingredients remaining and/or formation of substances from degradation of the ingredient can be determined by High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), Mass Spectrometry (MS), etc. The size of the encapsulated ingredient can be determined by dynamic light scattering (DLS), Scanning Electron Microscopy (SEM), cryogenic SEM (cryo-SEM), etc. The particle size (PSD), polydispersity index (PDI), and/or zeta potential (ZP) can be measured using batch mode dynamic light scattering (DLS) and electrophoretic mobility. Turbidity can be measured using a suitable turbidity meter, such as a HACH 2100N turbidimeter following ISO method 7027.

[00386] It is proposed that the reduction in turbidity of formulations caused by plant extract presence is due to the saponin content of the plant extract. In the cases presented here, plant extract saponin content was significant in all of them. Saponins are surfactant compounds, and surfactants have been demonstrated to reduce turbidity in many applications, including with emulsions. However, there are also many cases in which the presence of surfactants have been demonstrated to increase turbidity as well. The exact mechanism by which the presence of plant extracts with significant saponin content reduce the turbidity of the formulation in beer is unknown, but it may result from an overall decrease in particle size caused by the surfactant properties of the saponins of the plant extract.

Table 25

Table 25 (continued)

Table 26

5 Table 27

Table 28

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 28 (continued)

Table 29 - Foam decay rate data for formulation with added plant extract

Table 30 - Foam decay rate data for formulation without added plant extract

[00387] Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the design as defined by the appended claims.

Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the present disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps

Claims

WHAT IS CLAIMED IS:

1. A composition comprising a plurality of lipid nanoparticles comprising:

5 to 60 wt. % of at least one phosphatidylcholine;

0 to 40 wt. % of a bulking agent;

0.01 to 20 wt. % of an active agent; and

0. 1 to 20 wt. % of at least one plant extract.

2. The composition of claim 1, comprising:

5 to 30 wt. % of a phosphatidylcholine;

0 to 20 wt. % of a bulking agent;

0. 1 to 10 wt. % of an active agent;

0.5 to 10 wt. % of at least one plant extract; and 25.0 to 93.9 wt. % of water.

3. The composition of claim 1 or 2, wherein the composition does not include a bulking agent.

4. The composition of claim 1 or 2, wherein the composition comprises a bulking agent.

5. The composition of claim 4, wherein the composition comprises about 3.0 wt. % to about 9.0 wt. % of the bulking agent.

6. The composition of any one of claims 4 or 5, wherein the bulking agent comprises a carbohydrate and/or polymer.

7. The composition of claim 6, wherein the bulking agent comprises maltodextrin and/or mannitol.

8. The composition of any one of claims 1 to 7, wherein the at least one plant extract comprises an extract of Tribulus terrestris, Yucca schidigera, Quillaja saponaria, Camellia sinesis, and/or Glycyrrhiza glabra.

9. The composition of any one of claims 1 to 8, wherein the at least one plant extract comprises a de-oiled plant extract.

10. The composition of any one of claims 1 to 9, further comprising 1- Lysophosphatidylcholine (1-LPC), 2-Lysophosphatidylcholine (2-LPC), Phosphatidylethanolamine (PE), N-acylphosphatidylethanolamine (APE), Phosphatidylinositol (PI), and/or Phosphatidic acid (PA).

11. The composition of claim 10, wherein the concentration of PI and/or PE is significantly greater than the concentration of 1-LPC, 2-LPC, APE, and/or PA.

12. The composition of claim 10, wherein the concentration of 1-LPC, 2-LPC, PE, APE, PI, and/or PA are at or below l/10^ththe concentration of phosphatidylcholine.

13. The composition of any one of claims 1 to 12, comprising: about 0 wt. % to about 5.0 wt. % of an antioxidant.

14. The composition of any one of claims 1 to 13, comprising: about 0 wt. % to about 0.5 wt. % of an antioxidant.

15. The composition of any one of claims 1 to 14, wherein greater than about 80% of the active agent is comprised in a lipid nanoparticle.

16. The composition of any one of claims 1 to 15, wherein the composition further comprises at least one or more buffers, one or more solvents, and/or one or more preservatives.

17. The composition of claim 16, wherein the one or more buffers comprises sodium bicarbonate and/or sodium carbonate, the one or more solvents comprises ethanol, and the one or more preservatives comprises citric acid monohydrate, potassium sorbate, sodium benzoate, and/or a natural preservative.

18. The composition of claim 17, comprising: sodium bicarbonate at about 0.0015 wt % to about 0.06 wt.% and/or sodium carbonate at about 0.0015 wt % to about 0.06 wt. %; and citric acid monohydrate at about 0.003 wt. % to about 0.4 wt. %, potassium sorbate at about 0.003 wt. % to about 0.4 wt. %, sodium benzoate at about 0.003 wt. to about 0.4 wt %, and/or natural preservative at about 0.003 wt. % to about 2.0 wt. %.

19. The composition of any one of claims 17 to 18, wherein the natural preservative comprises a mushroom extract.

20. The composition of claim 19, wherein the mushroom extract is from a stem of a white button mushroom.

21. The composition of any one of claims 17 to 18, wherein the natural preservative comprises a fruit or berry extract.

22. The composition of claim 21, wherein the fruit or berry extract is a raspberry or rowanberry extract.

23. The composition of any one of claims 1 to 22, wherein the active agent comprises a hydrophilic active agent.

24. The composition of claim 23, wherein the hydrophilic active agent is a water-soluble vitamin.

25. The composition of claim 24, wherein the water-soluble vitamin is vitamin C or a B- vitamin.

26. The composition of any one of claims 1 to 25, wherein the active agent comprises a hydrophobic active agent.

27. The composition of any one of claims 1 to 26, wherein the active agent has a greater wt. % solubility in either water or ethanol than in medium chain triglycerides.

28. The composition of any one of claims 1 to 27, wherein the active agent comprises a polyphenol.

29. The composition of claim 28, wherein the polyphenol comprises trans-resveratrol.

30. The composition of any one of claims 28 to 29, wherein the polyphenol comprises dihydromyricetin .

31. The composition of any one of claims 1 to 30, wherein the active agent comprises a flavonoid.

32. The composition of claim 31, wherein the flavonoid is a prenylated flavonoid.

33. The composition of claim 32, wherein the prenylated flavonoid is xanthohumol.

34. The composition of claim 33, wherein the flavonoid xanthohumol is comprised in

XANTHOFLAV™, XANOHOP GOLD, and/or XANTHOFLAV™ PURE.

35. The composition of any one of claims 1 to 34, wherein the active agent comprises xanthohumol and additional hop prenylated flavonoids.

36. The composition of any one of claims 33 to 35, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of about 60%, for at least 1 month.

37. The composition of claim 35, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 4 months.

38. The composition of claim 35, wherein at least about 90% of the xanthohumol does not isomerize to isoxanthohumol when stored at 25 °C with a relative humidity of 60%, for at least 8 months.

39. The composition of any one of claims 1 to 38, wherein the weight ratio of the phosphatidylcholine to the active agent is about 12: 1 to about 3:2.

40. The composition of claim 39, wherein the weight ratio of the phosphatidylcholine to the active agent is about 11: 1 to about 5: 1.

41. The composition of any one of claims 1 to 40, wherein the phosphatidylcholine is from a sunflower.

42. The composition of claim 41, wherein the phosphatidylcholine comprises a compound with a structure of:

43. The composition of any one of claims 1 to 42, comprising:

5 to 25 wt. % of the phosphatidylcholine;

0. 1 to 10 wt. % of the active agent;

0 to 7.5 wt. % of the bulking agent; 2.5 to wt. 10 % of at least one plant extract; and

25 to 89.9 wt. % water.

44. The composition of any one of claims 1 to 43, comprising:

10 to 25 wt. % the phosphatidylcholine;

1 to about 2.5 wt. % of the active agent;

0 to 5 wt. % the bulking agent;

5 to wt. 10 % of at least one plant extract; and

50 to about 70 wt. % water.

45. The composition of any one of claims 1 to 44, consisting essentially of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and optionally the water.

46. The composition of any one of claims 43 or 44, consisting of the phosphatidylcholine, the active agent, the bulking agent, the at least one plant extract, and the water.

47. The composition of any one of claims 1 to 46, further comprising: about 0 wt. % to about 0.5 wt. % of an antioxidant.

48. The composition of any one of claims 1 to 47, wherein the composition comprises 0.01 to 5.0 wt. % of ethanol.

49. The composition of any one of claims 1 to 48, wherein the composition comprises 0.1 to 1.0 wt. % of ethanol.

50. The composition of any one of claims 1 to 49, wherein the bulking agent comprises a maltodextrin based bulking agent.

51. The composition of any one of claims 1 to 50, wherein the bulking agent comprises a mannitol based bulking agent.

52. The composition of any one of claims 1 to 51, wherein the plurality of lipid nanoparticles has an average density of about 0.993 g/cm³ to about 1.02 g/cm³.

53. The composition of any one of claims 1 to 52, wherein the lipid nanoparticles comprise liposomes and/or emulsion particles.

54. The composition of claim 53, wherein at least about 90 % of the plurality of lipid nanoparticles are liposomes.

55. The composition of any one of claims 1 to 54, wherein the plurality of lipid nanoparticles has an average size ranging from about 30 nanometers (nm) to about 200 nm.

56. The composition of any one of claims 1 to 55, wherein the plurality of lipid nanoparticles has an average size ranging from about 50 nm to about 150 nm.

57. The composition of any one of claims 1 to 56, wherein the plurality of lipid nanoparticles has an average size ranging from about 100 nm to about 150 nm.

58. The composition of any one of claims 1 to 57, wherein 25% to 100% of the lipid nanoparticles are liposomes.

59. The composition of any one of claims 1 to 58, wherein 50% to 100% of the lipid nanoparticles are liposomes.

60. The composition of any one of claims 1 to 59, wherein 75% to 100% of the lipid nanoparticles are liposomes.

61. The composition of any one of claims 1 to 60, wherein 95% to 100% of the lipid nanoparticles are liposomes.

62. The composition of any one of claims 1 to 61, wherein the active agent is comprised within either an inner surface of the nanoparticle, within an outer surface of the nanoparticle, and/or within a lipid bilayer of the nanoparticle.

63. The composition of claim 62, wherein the active agent is comprised within the lipid bilayer of the nanoparticle.

64. The composition of any one of claims 1 to 63, wherein the majority of nanoparticles are unilamellar.

65. The composition of any one of claims 1 to 64, comprising multilame liar nanoparticles.

66. The composition of any one of claims 1 to 65, wherein less than about 20% of the lipid nanoparticles are emulsion particles.

67. The composition of any one of claims 1 to 66, wherein less than about 10% of the lipid nanoparticles are emulsion particles.

68. The composition of any one of claims 1 to 67, having a turbidity of about 0 to about 5000 Nephelometric Turbidity Units (NTU) at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

69. The composition of any one of claims 1 to 68, having a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

70. The composition of any one of claims 1 to 69, having a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

71. The composition of any one of claims 1 to 70, having a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

72. The composition of any one of claims 1 to 71, having a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for about 1 month at a relative humidity of about 75%.

73. The composition of any one of claims 1 to 72, wherein the composition does not include a sterol and/or a triglyceride.

74. The composition of any one of claims 1 to 73, wherein the composition is free of synthetic surfactants and is free of synthetic emulsifiers at concentrations greater than about l/10^ththat of phosphatidylcholine.

75. The composition of claim 74, wherein the composition comprises less than about 2.5 wt. % of emulsifiers other than phosphatidylcholine.

76. The composition of any one of claims 1 to 75, wherein the composition is configured such that, upon storage for a period of one month at room temperature, the average size of the nanoparticles changes by less than about 20%.

77. The composition of any one of claims 1 to 76, wherein polydispersity index (PDI) of the plurality of lipid nanoparticles in the composition is about 0.01 to about 0.8.

78. The composition of any one of claims 1 to 77, wherein PDI of the plurality of lipid nanoparticles in the composition is about 0.05 to about 0.5.

79. The composition of any one of claims 1 to 78, wherein PDI of the plurality of lipid nanoparticles in the composition is about 0.1 to about 0.5.

80. An aqueous formulation comprising the composition of any one of claims 1 to 79.

81. The aqueous formulation of claim 80, wherein the composition is comprised in a second composition, and does not settle or separate from the second composition when stored for at least one month at a temperature of about 4 °C to about 20 °C.

82. The aqueous formulation of any one of claims 80 to 81, comprising 20 wt. % to about 99.0 wt. % of the lipid nanoparticles.

83. The aqueous formulation of any one of claims 80 to 82, comprising 50 wt. % to about 95.0 wt. % of the lipid nanoparticles.

84. The aqueous formulation of any one of claims 80 to 83, comprising 60.0 wt. % to about 80.0 wt. % of the lipid nanoparticles.

85. The aqueous formulation of any one of claims 80 to 81, comprising 8.0 wt. % to about 30.0 wt. % of the lipid nanoparticles.

86. The aqueous formulation of claim 85, comprising 17.0 wt. % to about 21.0 wt. % of the lipid nanoparticles.

87. The aqueous formulation of any one of claims 80 to 86, having a turbidity of about 0 to about 5000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 5000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

88. The aqueous formulation of any one of claims 80 to 87, having a turbidity of about 0 to about 2000 NTU at a temperature of about 4 °C and/or a turbidity of about 0 to about 2000 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

89. The aqueous formulation of any one of claims 80 to 88, having a turbidity of about 100 to about 1000 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 1000 NTU at a temperature of about 40 °C at a relative humidity of about

90. The aqueous formulation of any one of claims 80 to 89, wherein the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C at a relative humidity of about 75%.

91. The aqueous formulation of any one of claims 80 to 90, wherein the aqueous formulation has a turbidity of about 100 to about 500 NTU at a temperature of about 4 °C and/or a turbidity of about 100 to about 800 NTU at a temperature of about 40 °C, when stored for 1 month at a relative humidity of about 75%.

92. The aqueous formulation of any one of claims 80 to 91, wherein the aqueous formulation does not settle or separate when stored for at least one month at a temperature of about 20 °C

93. The aqueous formulation of any one of claims 80 to 92, wherein the aqueous formulation is configured such that, upon storage for a period of one month at room temperature, the average size of the plurality of lipid nanoparticles changes by less than about 20%.

94. The aqueous formulation of any one of claims 80 to 93, wherein polydispersity index (PDI) of the plurality of lipid nanoparticles in the aqueous formulation is about 0.01 to about 0.8.

95. The aqueous formulation of any one of claims 80 to 94, wherein PDI of the plurality of lipid nanoparticles in the aqueous formulation is about 0.05 to about 0.5.

96. The aqueous formulation of any one of claims 80 to 95, wherein PDI of the plurality of lipid nanoparticles in the aqueous formulation is about 0. 10 to about 0.5.

97. The aqueous formulation of any one of claims 80 to 96, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 20 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

98. The aqueous formulation of any one of claims 80 to 97, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 15 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

99. The aqueous formulation of any one of claims 80 to 98, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 10 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

100. The aqueous formulation of any one of claims 80 to 99, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 7 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

101. The aqueous formulation of any one of claims 80 to 100, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 4 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

102. The aqueous formulation of any one of claims 80 to 101, wherein the aqueous formulation maintains a turbidity of less than about 2.5 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

103. The aqueous formulation of any one of claims 80 to 102, wherein the aqueous formulation maintains a turbidity of less than about 1 EBC more than a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

104. The aqueous formulation of any one of claims 80 to 103, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 300% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

105. The aqueous formulation of any one of claims 80 to 104, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 250% that a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

106. The aqueous formulation of any one of claims 80 to 105, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 200% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

107. The aqueous formulation of any one of claims 80 to 106, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 150% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

108. The aqueous formulation of any one of claims 80 to 107, wherein the aqueous formulation maintains a turbidity (EBC) of less than about 125% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

109. The aqueous formulation of any one of claims 80 to 108, wherein the aqueous formulation maintains a turbidity of less than about 115% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

110. The aqueous formulation of any one of claims 80 to 109, wherein the aqueous formulation maintains a turbidity of less than about 110% that of a control second composition over 5 days at about 40 °C with about 75% relative humidity, where the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

111. The aqueous formulation of any one of claims 80 to 110, wherein the aqueous formulation maintains a turbidity (EBC) that does not significantly differ from the turbidity (EBC) of a control second composition over 5 days at about 40 °C with about 75% relative humidity, wherein the control second composition is the same as the aqueous formulation except that the control second composition does not comprise the plurality of lipid nanoparticles.

112. An ingestible composition comprising the composition of any one of claims 1 to 79.

113. The ingestible composition of claim 112, wherein the ingestible composition is a beverage.

114. The ingestible composition of any one of claims 112 to 113, comprising at least about 50.0 wt. % water.

115. The ingestible composition of any one of claims 112 to 114, wherein the ingestible composition is a fermented beverage.

116. The ingestible composition of any one of claims 112 to 115, wherein the ingestible composition is a carbonated beverage.

117. The ingestible composition of any one of claims 112 to 116, wherein ingestible composition is a beer.

118. The ingestible composition of claim 117, wherein the composition or aqueous composition reduces the formation of acetyl aldehyde or beta-damascenone in the beer.

119. The ingestible composition of any one of claims 112 to 118, wherein the composition does not include alcohol.

120. The ingestible composition of any one of claims 112 to 119, wherein the composition includes alcohol.

121. The ingestible composition of claim 120, wherein the composition comprises about 0.01 wt. % to about 10.0 wt % alcohol.

122. The ingestible composition of claim 121, wherein the composition comprises about 2.0 wt % to about 9.0 wt. % alcohol.

123. The ingestible composition of claim 122, wherein the composition comprises about 3.0 wt. % to about 8.0 wt. % alcohol.

124. The ingestible composition of any one of claims 112 to 123, wherein the composition comprises an aqueous formulation and the plurality of lipid nanoparticles.

125. The ingestible composition of any one of claims 112 to 124, wherein the ingestible composition comprises about 10 to about 20 milligrams of the plurality of lipid nanoparticles per about 1 gram of the ingestible composition.

126. The ingestible composition of any one of claims 112 to 125, wherein turbidity of the composition is not perceivable to the unaided eye.

127. The ingestible composition of any one of claims 112 to 126, wherein pH of the composition is about 2.5 to 9.5.

128. The ingestible composition of any one of claims 112 to 127, wherein pH of the composition is about 2.5 to about 7.5.

129. The ingestible composition of any one of claims 112 to 128, wherein pH of the composition is about 2.5 to about 7.0.

130. The ingestible composition of any one of claims 112 to 129, wherein pH of the composition is about 2.5 to about 6.7.

131. The ingestible composition of any one of claims 112 to 130, wherein the foam decay rate of the composition is slower than that of a similar ingestible composition which does not contain plant extract.

132. The ingestible composition of any one of claims 112 to 131, wherein the foam decay rate of the composition is slower than 75% that of a similar ingestible composition which does not contain plant extract.

133. The ingestible composition of any one of claims 112 to 132, wherein the foam decay rate of the composition is slower than 50% that of a similar ingestible composition which does not contain plant extract.

134. A method of making the ingestible composition of any one of claims 112 to 133, the method comprising combining the composition of any one of claims 1 to 79 with an ingestible item.

135. The method of claim 134, wherein the ingestible item is a beverage.

136. The method of claim 135, wherein the beverage is a beer.

137. The method of any one of claims 135 to 136, wherein the ingestible composition comprises about 10 to about 20 milligrams of the plurality of lipid nanoparticles per about 1 gram of the ingestible item.

138. A method of ingesting the ingestible composition of any one of claims 112 to 137 by a subject, the method comprising ingesting the ingestible composition.

139. The method of claim 138, wherein ingesting the ingestible composition prevents or treats cancer in the subject.

140. The method of any one of claims 138 to 139, wherein ingesting the ingestible composition prevents or treats inflammation in the subject.

141. The method of any one of claims 138 to 140, wherein ingesting the ingestible composition reduces low -density lipoprotein levels and/or increases high-density lipoprotein levels in the subject.

142. The method of any one of claims 138 to 141, wherein ingesting the ingestible composition aids in recovery from a SARS-CoV-2 infection in the subject.

143. A method of preserving a perishable composition, the method comprising combining the composition of any one of claims 1 to 79 to the perishable composition, wherein the composition preserves the perishable composition.

144. The method of claim 143, wherein the perishable composition is an ingestible composition.

145. The method of claim 144, wherein the perishable composition is atopical skin composition.

146. A topical skin care composition comprising the composition of any one of claims 1 to 79.

147. The topical skin care composition of claim 146, wherein the topical skin care composition is an emulsion.

148. The topical skin care composition of claim 147, wherein the emulsion is an oil-in- water emulsion.

149. The topical skin care composition of any one of claims 146 to 148, wherein the topical skin care composition comprises at least about 50.0 wt. % water.

150. The topical skin care composition of any one of claims 146 to 149, wherein the plurality of lipid nanoparticles is comprised within an aqueous phase of the topical skin care composition.

151. A method of applying the topical skin care composition of any one of claims 146 to 150 to skin, the method comprising applying the topical skin care composition to the skin.

152. The method of claim 151, further comprising treating a skin condition.

153. The method of claim 152, wherein the skin condition is a fine line, a wrinkle, uneven skin tone, hyperpigmented skin, or inflamed skin.

154. The method of any one of claims 151 to 153, wherein the topical skin care composition reduces skin inflammation.