Decisive Role of HydrophobicSide Groups of Polypeptidesin Thermosensitive Gelation.

Thermosensitive hydrogels based on PEG and poly(l-glutamate)sbearing different hydrophobic side groups were separately synthesizedby the ring-opening polymerization (ROP) of l-glutamate N-carboxyanhydrides containing different alkyl protectedgroups, that is, methyl, ethyl, n-propyl, and n-butyl, using mPEG45-NH2as macroinitiator.The resulting copolymers underwent sol–gel transitions in responseto temperature change. Interestingly, the polypeptides containingmethyl and ethyl showed significantly lower critical gelation temperatures(CGTs) than those bearing n-propyl and butyl sidegroups. Based on the analysis of 13C NMR spectra, DLS,circular dichroism spectra, and ATR-FTIR spectra, the sol–geltransition mechanism was attributed to the dehydration of poly(ethyleneglycol) and the increase of β-sheet conformation content inthe polypeptides. The in vivo gelation test indicated that the copolymersolution (6.0 wt %) immediately changed to a gel after subcutaneousinjection into rats. The mass loss of the hydrogel in vitro was acceleratedin the presence of proteinase K, and the MTT assay revealed that theblock copolymers exhibited no detectable cytotoxicity. The presentwork revealed that subtle variation in the length of a hydrophobicside group displayed the decisive effect on the gelation behaviorof the polypeptides. In addition, the thermosensitive hydrogels couldbe promising materials for biomedical applications due to their goodbiocompatibility, biodegradability, and the fast in situ gelationbehavior. [ABSTRACT FROM AUTHOR]