Dual-Crosslinked Human Serum Albumin-Polymer Hydrogels for Affinity-Based Drug Delivery

作者：Noteborn Willem E M; Gao Yue; Jesse Wim; Kros Alexander; Kieltyka Roxanne E^*

来源：Macromolecular Materials and Engineering, 2017, 302(10): 1700243.

DOI：10.1002/mame.201700243

• affinity-based drug release
• crosslinking
• human serum albumin
• hydrogel

A dual-crosslinked in situ gelling drug delivery scaffold based on dextran (DEX), thiolated serum albumin, and poly(ethylene glycol) (PEG) is presented. Dextran-vinyl sulfone conjugates with varied molecular weight and degrees of substitution are synthesized by controlling the reaction time and temperature with divinyl sulfone. Dextran-human serum albumin (sHSA) hydrogels are prepared using a thiol-vinyl sulfone Michael addition reaction with thiolated albumin as the crosslinker. Poly(ethylene glycol) dithiol is added as a third component to the crosslinked dextran-human serum albumin hydrogel to facilitate additional crosslinking, and reduce gelation time, while modulating the physicochemical properties of the Dex-sHSA-PEG network. The onset of gelation of the modular three-component dual-crosslinked hydrogel network ranges from 45 min to 1.5 h depending on gel constituent concentrations and the gelation temperature (25 or 37 degrees C). All gels remain stable for over a 25 d period under physiological conditions. In vitro drug release assays show that dual-crosslinked Dex-sHSA-PEG hydrogels can deliver doxorubicin in a sustained manner over 7 d. Finally, a Tetrazolium-based assay shows the biocompatible nature of the Dex-sHSA-PEG hydrogels and capacity to deliver doxorubicin successfully to MCF-7 breast cancer cells.

• 出版日期2017-10