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

Abstract

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) andligand-responsive calmodulin (CalM) were genetically engineered, over-expressed, and nonchromatographically purified by inversetransition cycling. Diluted EBP-CalM-EBP (ECE) triblock copolypeptides under physiological conditions self-assembled intovesicles 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 inphysically crosslinked hydrogels. They showed controlled rheological and mechanical properties depending on the conformationalchange of the CalM middle block induced by binding either Ca2+or Ca2+and trifluoperazines (TFPs) as ligands. In addition, bothCa2+-free and Ca2+-bound ECE triblock copolypeptide hydrogels exhibited biocompatibility, while those bound to both Ca2+andTFPs showed severe cytotoxicity because of controlled TFP release of the CalM blocks. The ECE triblock hydrogels with stimuliresponsiveness would be useful as injectable drug delivery depots for biomedical applications