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Mucoadhesive nanoparticle delivery system

A nanoparticle, mucosal technology, applied in respiratory system diseases, urinary system diseases, cardiovascular system diseases, etc., can solve non-specific problems

Active Publication Date: 2015-04-08
UNIVERSITY OF WATERLOO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The main disadvantage of physical interactions is that they are non-specific and much weaker than covalent interactions

Method used

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  • Mucoadhesive nanoparticle delivery system
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  • Mucoadhesive nanoparticle delivery system

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specific Embodiment approach

[0249] In some embodiments, there is provided a nanoparticle composition for delivering a payload to a mucosal site, the nanoparticle comprising a plurality of amphiphilic macromolecules comprising: a hydrophobic moiety comprising polylactide, polyethylene Biocompatible polymers of lactide, poly(lactide-co-glycolide), poly(ε-caprolactone), or combinations thereof; hydrophilic moieties comprising polysaccharides, polynucleotides, polypeptides or A biocompatible polymer of its combination, the hydrophilic portion includes a plurality of functional moieties; and a mucosal targeting portion selected from phenylboronic acid (PBA) derivatives, thiol derivatives or acrylate derivatives, wherein the hydrophilic At least a portion of the functional moiety of the moiety is conjugated to a mucosal targeting moiety.

[0250] In some embodiments, there is provided a nanoparticle composition for delivering a payload to a mucosal site, the nanoparticle comprising a plurality of amphiphilic m...

Embodiment 1

[0261] Synthesis and characterization of embodiment 1.Dex-b-PLA

[0262] 1.1 Materials

[0263] Acid-terminated poly(D,L-lactide) (PLA, M w ~10, 20 and 50kDa) and PLGA-PEG (PLGA M w ~40kDa, PEG M w ~6 kDa) were purchased from Lakeshore Biomaterials (Birmingham, AL, USA). PLA was purified by dissolving PLA in dimethylsulfoxide (DMSO) and precipitating in methanol to remove residual monomers. Dextran (Dex, M r ~1.5, 6, and 10 kDa), hydrochloric acid (HCl), triethylamine (TEA), N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC), and sodium cyanoborohydride (NaCNBH 3 ) were purchased from Sigma Aldrich (Oakville, ON, Canada) and used without further purification. N-Hydroxysulfosuccinimide (thio-NHS) and N-tert-butoxycarbonylethylenediamine were purchased from CNH Technologies (Massachusetts, USA). Deprotonate doxorubicin-HCl (MW=580 Da, Intatrade GmBH, Bitterfield, Germany) by adding TEA (2M equiv.) in aqueous doxorubicin-HCl solution and extract with dichloromethane (DCM...

Embodiment 2

[0278] Example 2. Encapsulation and in vitro of doxorubicin in Dex-b-PLA NP by nanoprecipitation method

[0279] Encapsulation of doxorubicin in Dex-b-PLA NPs was accomplished using the nanoprecipitation method. Both Dex-b-PLA and doxorubicin were dissolved in DMSO (7 mg / mL Dex-b-PLA concentration, varying drug concentrations). 1 mL of the DMSO solution was added to 10 mL of water in a dropwise fashion with stirring, and stirring was continued for an additional 30 minutes. NPs in water were filtered through syringe filters (pore size = 200 nm) to remove drug aggregates, and then filtered through ultrafiltration filter tubes (MWCO = 10 kDa, Millipore) to remove any remaining free drug in suspension. Filtered NPs containing encapsulated doxorubicin were resuspended and diluted in DMSO. Therefore, the drug loading (wt %) in the polymer matrix was calculated by measuring the concentration of doxorubicin in the mixture by obtaining the absorbance of the solution at 480 nm using a...

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Abstract

The present disclosure relates generally to a mucoadhesive nanoparticle delivery system. The nanoparticles are formed from amphiphilic macromolecules conjugated to a mucosal targeting moiety in such a manner that the surface of the nanoparticle is coated with the targeting moiety. The surface density of the targeting moiety can be tuned for adjustable targeting of the nanoparticles to a mucosal site without substantially compromising the stability of the particles. The particles were found to have high loading efficiency and sustained release properties at the mucosal site. The present disclosure also relates to polymers and macromolecules useful in the preparation of the mucoadhesive nanoparticles, as well as compositions, methods, commercial packages, kits and uses related thereto.

Description

[0001] Cross reference to related applications [0002] This application claims the benefit of priority to US Provisional Patent Application No. 61 / 690,127, filed June 20, 2012, which is incorporated herein by reference in its entirety. technical field [0003] The present disclosure generally relates to mucoadhesive nanoparticle delivery systems. Nanoparticles can be tuned for controlled targeting and adhesion of nanoparticles at mucosal sites without substantially compromising particle stability. The present disclosure also relates to components for preparing nanoparticles, and compositions, methods, processes, commercial packages, kits and uses related thereto. Background technique [0004] Drug delivery to patients with controlled release of active ingredients has been an area of ​​active research for decades and is driven by many recent studies in polymer science. Controlled release polymer systems can be designed to provide drug levels within an optimal range over a ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/34A61K47/36A61K9/50A61K9/52
CPCA61K9/006A61K47/48915A61K47/48907A61K31/704A61K31/69A61K47/48092A61K47/48023A61K45/06A61K47/48923A61K47/26A61K31/131A61K31/78A61K9/5153A61K49/0002A61K47/54A61K47/549A61K47/6935A61K47/6937A61K47/6939A61K38/13Y10T428/2982A61P1/02A61P1/04A61P1/06A61P1/08A61P1/10A61P1/12A61P1/16A61P11/00A61P11/02A61P11/04A61P11/06A61P11/10A61P11/14A61P13/10A61P15/00A61P15/02A61P15/16A61P15/18A61P17/04A61P19/02A61P19/06A61P21/02A61P25/02A61P25/04A61P25/06A61P25/16A61P25/18A61P25/20A61P25/24A61P25/26A61P25/28A61P27/02A61P27/04A61P27/06A61P27/12A61P27/14A61P29/00A61P3/02A61P3/04A61P3/12A61P31/00A61P31/04A61P31/10A61P31/12A61P31/16A61P31/22A61P33/00A61P33/10A61P35/00A61P35/02A61P3/06A61P37/06A61P37/08A61P43/00A61P5/00A61P5/30A61P5/38A61P7/02A61P7/10A61P7/12A61P9/00A61P9/04A61P9/06A61P9/08A61P9/10A61P9/12A61P3/10Y02A50/30A61K9/5123A61K9/5161A61K9/5192
Inventor 弗兰克·古林登·威廉·詹姆士·琼斯刘圣彦
Owner UNIVERSITY OF WATERLOO
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