Controllable multi-phase protein release from in-situ hydrolyzable hydrogel
Chi Ming Laurence Lau1, Ghodsiehsadat Jahanmir2, Yu Yu3
1Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, China; The Hong Kong University of Science and Technology Shenzhen Research Institute, Shenzhen, China.
Summary
This study introduces new dextran-based hydrogels for controlled, long-term protein release, overcoming common issues like burst release and drug dumping for biomedical applications.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- Controlling long-term protein release from hydrogels, especially in-situ forming ones, faces challenges like initial burst release, subsequent release cessation, and late-stage drug dumping.
- Existing hydrogel depots often struggle to provide predictable and sustained therapeutic protein delivery over extended periods.
Purpose of the Study:
- To develop hydrolyzable dextran-based hydrogels using Michael addition crosslinking to provide a systematic solution for controlled, long-term protein release.
- To engineer hydrogel properties by tuning polymer concentration, crosslinking density, and ester linker hydrolysis rates to achieve tunable release profiles.
- To demonstrate sustained and adjustable release of various model proteins for potential biomedical applications.
Main Methods:
- Synthesized dextran-based hydrogels crosslinked via Michael addition, incorporating ester linkers with tunable hydrolysis rates (4 hours to 4 months).
- Investigated the effect of polymer concentration on initial protein trapping and release.
- Modulated hydrogel meshwork dynamics using crosslinking density and ester linker cleavage rates.
- Evaluated controlled release of proteins of varying sizes (lysozyme, BSA, IgG, bevacizumab).
- Developed tunable multi-phase release profiles by incorporating mixtures of ester linkers with different half-lives.
Main Results:
- Achieved controlled release of model proteins, including sustained release of immunoglobulin G (IgG) from 10 days to 8 months.
- Demonstrated that polymer concentration dictates the initial proportion of trapped versus releasable protein.
- Showcased tunable multi-phase release profiles by adjusting the type and ratio of incorporated ester linkers.
- Successfully controlled protein release duration and fraction through linker half-life and mixing ratios.
Conclusions:
- The developed hydrolyzable dextran-based hydrogels offer a versatile platform for achieving long-term and adjustable protein release.
- This hydrogel system effectively addresses the limitations of conventional hydrogel depots, paving the way for advanced biomedical applications.
- The ability to fine-tune release kinetics through linker design provides a powerful tool for optimizing protein therapeutics delivery.
