Ki Hyun Bae, Fan Lee, Keming Xu, Choong Tat Keng, Sue Yee Tan, Yee Joo Tan, Qingfeng Chen, Motoichi Kurisawa, Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs, Biomaterials, Volume 63, 2015, Pages 146-157, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2015.06.008.
Abstract:
Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research is supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research (A*STAR), Singapore).