[go: up one dir, main page]

WO2025151105A1 - Nanoparticule chargée d'acide gentisique et de 5-fluorouracile revêtue de biotine - Google Patents

Nanoparticule chargée d'acide gentisique et de 5-fluorouracile revêtue de biotine

Info

Publication number
WO2025151105A1
WO2025151105A1 PCT/TR2024/051956 TR2024051956W WO2025151105A1 WO 2025151105 A1 WO2025151105 A1 WO 2025151105A1 TR 2024051956 W TR2024051956 W TR 2024051956W WO 2025151105 A1 WO2025151105 A1 WO 2025151105A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluorouracil
nanoparticles
biotin
gentisic acid
coating
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/TR2024/051956
Other languages
English (en)
Inventor
Banu MANSUROĞLU
Fatma Şayan POYRAZ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yildiz Teknik Universitesi
Yildiz Teknoloji Transfer Ofisi AS
Original Assignee
Yildiz Teknik Universitesi
Yildiz Teknoloji Transfer Ofisi AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from TR2024/000211 external-priority patent/TR2024000211A2/tr
Application filed by Yildiz Teknik Universitesi, Yildiz Teknoloji Transfer Ofisi AS filed Critical Yildiz Teknik Universitesi
Publication of WO2025151105A1 publication Critical patent/WO2025151105A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5123—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • polymeric carrier systems are used in cancer treatment as an alternative to traditional treatments such as radiotherapy and chemotherapy, which have high side effects.
  • the polymers supplied for polymeric carrier systems are selected among polymers that are biocompatible, biodegradable, do not cause antigenic response and can be excreted from the body.
  • PLGA poly(lactic-co-glycolic acid)
  • approved by the EMA and FDA may be a preferred polymer for polymeric carrier systems.
  • PLGA is synthesized by ring opening co-polymerization of two different monomers, cyclic dimers of glycolic acid and lactic acid (l,4-dioxane-2, 5-diones). For this reason, PLGA should be preferred for use in various applications by considering the lactic acid/glycolic acid ratio.
  • surface-active components e.g. polyvinyl alcohol (PVA)
  • PVA polyvinyl alcohol
  • the surface properties of nanoparticles can be modified by coating with various agents. After the coating process, the nanoparticular system can ensure targeting and controlling the release of the drug active substance it carries.
  • the main objective for the synthesis of nanoparticles with various chemical and physical properties is to obtain a population of particles with a uniform distribution, i.e. a particle population with similar surface charge and zeta potential.
  • the methods used in nanoparticle production e.g. solvent volatilization, ionic gelation
  • Gentisic acid a metabolite of aspirin, is a phenolic compound with a molecular weight of 154.12 g/mol containing two (-OH) groups at para positions.
  • Gentisic acid is a bioactive compound with a broad pharmacological spectrum, e.g. analgesic, antiarthritic, anti-inflammatory, antimutagenic, anticancer, antirheumatic, antispasmodic, antioxidant, antiparkinsonian, antifungal, siderophoricantigenotoxic activity. In addition, it may provide iron chelating and fibroblast growth factor (FGF) inhibition.
  • FGF fibroblast growth factor
  • Today, gentisic acid is preferred in cardiovascular applications due to its antioxidant activity and free radical scavenging properties.
  • 5-fluorouracil is an antimetabolite that acts as a pyrimidine antagonist and is an anticancer agent.
  • the mechanism of action of 5-fluorouracil is to interfere with DNA synthesis and mRNA translation.
  • the active substance 5-fluorouracil has three mechanisms of action, as follows:
  • FdUMP fluorodeoxyuridine monophosphate
  • TS thymidylacetase
  • This competition leads to a decrease in the production of thymidine, which is formed as a result of the combination of thymine, one of the four organic bases in the structure of DNA, and deoxyribose sugar, and thus cell proliferation.
  • the 5-fluorouracil metabolite interferes with DNA replication, the process by which the DNA molecule copies itself and doubles its amount.
  • 5-fluorouracil is also effective against precancerous skin lesions, actinic keratosis, viral warts and basal cell carcinoma.
  • the 5-Fluorouracil molecule kills both cancerous and healthy cells in the body, even at the lowest doses (i.e. minimum dose) expected to ensure its effectiveness.
  • Studies conducted by developing oral and topical dosage forms of the active substance 5-fluorouracil have concluded that the active substance has low bioavailability (i.e. the amount of the drug that can reach the target area from the application area) and low permeability (i.e. absorption to the applied area).
  • Biotin also known as vitamin H and vitamin B 7 in the literature, supports cellular growth. Its growthenhancing effect on cancer cells is higher compared to healthy cells. When cancer cells exhibit excessive growth as a result of biotin exposure, biotin-specific receptors are also overexpressed on the cancer cell surface. The specific interaction between biotin and receptors expressed on the cancer cell surface may enable targeted drug delivery.
  • the primary object of the invention is to overcome deficiencies in the state of the art.
  • Another object of the invention is to provide a targeted nanoparticle.
  • the development subject to the present application comprises one or more nanoparticles comprising 5-fluorouracil and gentisic acid, provided with one or more coatings comprising biotin, said one or more nanoparticles may be considered as a nanoparticular system.
  • the active ingredients are synthesized in the form encapsulated in nanoparticular carriers to increase the solubility and bioavailability of 5-fluorouracil and gentisic acid and to reduce their cytotoxicity.
  • the 5-fluorouracil and gentisic acid encapsulated nanoparticles obtained after encapsulation, furnished with one or more biotin-containing coatings, are adapted to target the cancer cells to which they are to be applied.
  • Receptors on the surface of cancer cells are able to recognize and directly bind to various targeting molecules.
  • nanoparticles encapsulated with the active ingredient of the drug cancer cells can be eliminated.
  • Nanoparticles developed as carrier and targeting systems can be made specific to cancer types with the surface modification described below.
  • DAPI i.e., 4',6-diamidino-2- phenylindole

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente demande concerne une ou plusieurs nanoparticules comprenant du 5-fluorouracile et de l'acide gentisique, dotées d'un ou de plusieurs revêtements comprenant de la biotine. La présente demande porte également sur un ou plusieurs procédés de fabrication de nanoparticules comprenant les étapes consistant à utiliser du 5-fluorouracile, de l'acide gentisique et de la biotine, à encapsuler le 5-fluorouracile et l'acide gentisique utilisés, ce qui permet d'obtenir une ou plusieurs nanoparticules comprenant du 5-fluorouracile et de l'acide gentisique, à utiliser un mélange de revêtement comprenant de la biotine, à revêtir une ou plusieurs nanoparticules encapsulées avec du 5-fluorouracile et de l'acide gentisique à l'aide du mélange de revêtement utilisé, ce qui permet d'obtenir une ou plusieurs nanoparticules pourvues d'un ou de plusieurs revêtements contenant de la biotine et contenant du 5-fluorouracile et de l'acide gentisique.
PCT/TR2024/051956 2024-01-09 2024-12-31 Nanoparticule chargée d'acide gentisique et de 5-fluorouracile revêtue de biotine Pending WO2025151105A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2024000211 2024-01-09
TR2024/000211 TR2024000211A2 (tr) 2024-01-09 Biyotin ile kaplanmış 5-florourasil ve gentisik asit yüklü nanopartikül.

Publications (1)

Publication Number Publication Date
WO2025151105A1 true WO2025151105A1 (fr) 2025-07-17

Family

ID=96387419

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2024/051956 Pending WO2025151105A1 (fr) 2024-01-09 2024-12-31 Nanoparticule chargée d'acide gentisique et de 5-fluorouracile revêtue de biotine

Country Status (1)

Country Link
WO (1) WO2025151105A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060127310A1 (en) * 2002-11-21 2006-06-15 Access Pharmaceuticals Australia Pty Ltd. Amplification of biotin-mediated targeting
US20110262490A1 (en) * 2009-03-30 2011-10-27 Jerry Zhang Polymer-agent conjugates, particles, compositions, and related methods of use
US20130202659A1 (en) * 2012-01-31 2013-08-08 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
US20140037553A1 (en) * 2012-07-27 2014-02-06 Industry Foundation Of Chonnam National University Bacterium-based microrobot capable of targeting cancer tissue

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060127310A1 (en) * 2002-11-21 2006-06-15 Access Pharmaceuticals Australia Pty Ltd. Amplification of biotin-mediated targeting
US20110262490A1 (en) * 2009-03-30 2011-10-27 Jerry Zhang Polymer-agent conjugates, particles, compositions, and related methods of use
US20130202659A1 (en) * 2012-01-31 2013-08-08 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
US20140037553A1 (en) * 2012-07-27 2014-02-06 Industry Foundation Of Chonnam National University Bacterium-based microrobot capable of targeting cancer tissue

Similar Documents

Publication Publication Date Title
Khan et al. Nano-co-delivery of berberine and anticancer drug using PLGA nanoparticles: exploration of better anticancer activity and in vivo kinetics
Rajan et al. Formation and characterization of chitosan-polylacticacid-polyethylene glycol-gelatin nanoparticles: A novel biosystem for controlled drug delivery
Sepehri et al. SN38 polymeric nanoparticles: in vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan
Ding et al. Tumor targeted nanostructured lipid carrier co-delivering paclitaxel and indocyanine green for laser triggered synergetic therapy of cancer
Khaira et al. Development and characterization of nanoparticles for the delivery of gemcitabine hydrochloride
Chaurasia et al. Lipopolysaccharide based oral nanocarriers for the improvement of bioavailability and anticancer efficacy of curcumin
Upadhyay et al. Conjugated and entrapped HPMA-PLA nano-polymeric micelles based dual delivery of first line anti TB drugs: improved and safe drug delivery against sensitive and resistant Mycobacterium tuberculosis
CN101984958B (zh) 纳米级阿苯达唑微粉及其制备方法
CN107126426B (zh) 一种盐酸阿霉素自组装聚合物纳米粒及其制备方法
Radwan et al. Development and evaluation of letrozole-loaded hyaluronic acid/chitosan-coated poly (d, l-lactide-co-glycolide) nanoparticles
Sun et al. Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors
Nesalin et al. Preparation and evaluation of chitosan nanoparticles containing zidovudine
Khan et al. NIR-light-triggered delivery of doxorubicin-loaded PLGA nanoparticles for synergistic cancer therapy on DMBA/TPA induced tumor-bearing mice
WO2019007019A1 (fr) Préparation de nanoparticules polymères de psoralène et procédé de préparation associé
Lv et al. “Carrier–drug” layer-by-layer hybrid assembly of biocompatible polydopamine nanoparticles to amplify photo-chemotherapy
Kzar et al. Everolimus loaded NPs with FOL targeting: preparation, characterization and study of its cytotoxicity action on MCF-7 breast cancer cell lines
Zhao et al. Engineering of hybrid anticancer drug-loaded polymeric nanoparticles delivery system for the treatment and care of lung cancer therapy
Baviskar et al. Development and evaluation of N-acetyl glucosamine-decorated vitamin-E-based micelles incorporating resveratrol for cancer therapy
CN109260177B (zh) 一种盐酸小檗碱复合物纳米粒的制备方法及其应用
Jia et al. Preparation, physicochemical characterization and cytotoxicity in vitro of gemcitabine-loaded PEG-PDLLA nanovesicles
Feng et al. Phenylboronic acid‐functionalized F127‐oligochitosan conjugate micelles for doxorubicin encapsulation
CN117018222A (zh) 一种活细胞药物递送系统及其制备方法和用途
Das et al. Formulation and in vitro evaluation of poly-(D, L-lactide-co-glycolide)(PLGA) nanoparticles of ellagic acid and its effect on human breast cancer, MCF-7 cell line
Naik et al. Formulation and evaluation of poly (L-lactide-co-[epsilon]-caprolactone) loaded gliclazide biodegradable nanoparticles as a control release carrier
Elbehairi et al. Encapsulation of ellagic acid in di-block copolymeric micelle for non-small cell lung cancer therapy

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24917535

Country of ref document: EP

Kind code of ref document: A1