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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Disulfide cross-linked polymer capsules: en route to biodeconstructible systems
Alexander N Zelikin1, John F Quinn, Frank Caruso
1Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
Researchers created stable multilayer thin films using poly(vinylpyrrolidone) and poly(methacrylic acid). These films, functionalized with cysteamine and cross-linked via disulfide bonds, demonstrated controlled drug release triggered by dithiothreitol (DTT).
Area of Science:
- Materials Science
- Biomaterials Engineering
- Polymer Chemistry
Background:
- Multilayer thin films offer versatile platforms for drug delivery and biomaterial applications.
- Controlling film stability at physiological conditions is crucial for in vivo applications.
- Thiol-functionalized polymers provide opportunities for cross-linking and triggered disassembly.
Purpose of the Study:
- To construct stable hydrogen-bonded multilayer thin films using poly(vinylpyrrolidone) and poly(methacrylic acid) functionalized with cysteamine.
- To investigate the stability of these films at physiological pH and their potential for drug retention and release.
- To explore the use of disulfide bond formation for enhanced film stability and dithiothreitol (DTT)-triggered disassembly.
Main Methods:
- Construction of multilayer thin films via hydrogen bonding between poly(vinylpyrrolidone) and poly(methacrylic acid).
- Functionalization with cysteamine to introduce thiol moieties.
- Cross-linking of thiol moieties to form disulfide bonds for enhanced stability.
- Quartz crystal microgravimetry (QCM) for monitoring film buildup and stability.
- Confocal microscopy for visualizing films on colloidal substrates.
- Drug retention and release studies using fluorescently labeled transferrin.
Main Results:
- Stable multilayer thin films were successfully constructed and characterized.
- Disulfide bond formation significantly improved film stability at physiological pH (7).
- Films remained intact at pH 7, with swelling observed, while disulfide-free films deconstructed.
- Dithiothreitol (DTT) triggered the disassembly of disulfide-bonded films.
- The films demonstrated the ability to retain and release a model drug (transferrin) upon DTT addition.
Conclusions:
- Hydrogen-bonded multilayer thin films functionalized with cysteamine and cross-linked via disulfide bonds offer enhanced stability at physiological pH.
- These films can act as drug delivery systems with triggered release capabilities mediated by thiol-disulfide exchange.
- The approach holds promise for in vivo applications, such as hollow capsules, leveraging intracellular protein-assisted deconstruction.
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