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Thiol-functionalized polymeric micelles: from molecular recognition to improved mucoadhesion
Marie-Hélène Dufresne1, Marc A Gauthier, Jean-Christophe Leroux
1Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal (QC), Canada, H3C 3J7.
Bioconjugate Chemistry
|July 21, 2005
Summary
This study introduces a novel method for creating targeted drug delivery systems using functionalized polyion complex micelles. These advanced micelles offer improved mucoadhesion and stimuli-responsive properties for enhanced therapeutic applications.
Area of Science:
- Polymer Chemistry
- Nanotechnology
- Biomedical Engineering
Background:
- Surface-modified colloids are promising for targeted drug delivery.
- Preparing targeted polyion complex micelles is challenging due to side reactions.
Purpose of the Study:
- To develop an innovative synthetic strategy for creating functionalized polyion complex micelles.
- To demonstrate the utility of thiol-functionalized copolymers for drug delivery applications.
Main Methods:
- Synthesized an asymmetric poly(ethylene glycol)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate) copolymer with a terminal thiol group.
- Functionalized the copolymer with biotin and self-assembled it with oligonucleotides to form polyion complex micelles.
- Investigated mucoadhesion and stimuli-responsive properties of the prepared micelles.
Main Results:
- Thiol groups enabled selective and quantitative reaction with maleimides under physiological conditions.
- Biotin-capped micelles demonstrated molecular recognition toward streptavidin.
- Thiol-decorated micelles exhibited enhanced mucoadhesion via disulfide bonds with mucin.
- Oxidative conditions induced intermicellar disulfide bonds, forming stimuli-responsive networks.
Conclusions:
- The proposed synthetic strategy overcomes challenges in preparing targeted polyion complex micelles.
- Thiol-functionalized micelles offer versatile platforms for drug delivery, mucoadhesion, and stimuli-responsive applications.