Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs.

Ki Hyun Bae, Fan Lee, Keming Xu, Choong Tat Keng, Sue Yee Tan, Yee Joo Tan, Qingfeng Chen, Motoichi Kurisawa

Index: Biomaterials 63 , 146-57, (2015)

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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. Copyright © 2015 Elsevier Ltd. All rights reserved.