Injectable Hydrogels of Stimuli-Responsive Elastin and Calmodulin-Based Triblock Copolypeptides for Controlled Drug Release.

Biomacromolecules

Department of Bionano Engineering and Department of Bionanotechnology, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan 15588, Republic of Korea.

Published: May 2022

A variety of block copolypeptides with stimuli responsiveness have been of growing interest for dynamic self-assembly. Here, multistimuli-responsive triblock copolypeptides composed of thermosensitive elastin-based polypeptides (EBP) and ligand-responsive calmodulin (CalM) were genetically engineered, over-expressed, and nonchromatographically purified by inverse transition cycling. Diluted EBP-CalM-EBP (ECE) triblock copolypeptides under physiological conditions self-assembled into vesicles at the nanoscale by temperature-triggered aggregation of the EBP block with lower critical solution temperature behaviors. Furthermore, concentrated ECE triblock copolypeptides under identical conditions exhibited thermally induced gelation, resulting in physically crosslinked hydrogels. They showed controlled rheological and mechanical properties depending on the conformational change of the CalM middle block induced by binding either Ca or Ca and trifluoperazines (TFPs) as ligands. In addition, both Ca-free and Ca-bound ECE triblock copolypeptide hydrogels exhibited biocompatibility, while those bound to both Ca and TFPs showed severe cytotoxicity because of controlled TFP release of the CalM blocks. The ECE triblock hydrogels with stimuli responsiveness would be useful as injectable drug delivery depots for biomedical applications.

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Source
http://dx.doi.org/10.1021/acs.biomac.2c00053DOI Listing

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