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Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs
- Bae, Ki Hyun, Lee, Fan, Xu, Keming, Keng, Choong Tat, Tan, Sue Yee, Tan, Yee Joo, Chen, Qingfeng, Kurisawa, Motoichi
- Biomaterials 2015 v.63 pp. 146-157
- animal models, bioactive properties, dextran, drugs, encapsulation, half life, hepatitis, hydrocolloids, interferons, microstructure, proteins
- 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.