Multi-responsive polypeptide hydrogels derived from N–carboxyanhydride terpolymerizations for delivery of nonsteroidal anti-inflammatory drugs (NSAIDs)

摘要

A polypeptide-based hydrogel system, when prepared from a diblock polymer with a ternary copolypeptide as one block, exhibited thermo-, mechano- and enzyme-responsive properties, which enabled the encapsulation of naproxen (Npx) during the sol–gel transition and its release in the gel state. Statistical terpolymerizations of l-alanine (Ala), glycine (Gly) and l–isoleucine (Ile) NCAs at a 1:1:1 feed ratio initiated by monomethoxy monoamino-terminated poly(ethylene glycol) afforded a series of methoxy poly(ethylene glycol)-block-poly(l-alanine-co-glycine-co-l-isoleucine) (mPEG-b-P(A-G-I)) block polymers. β-Sheets were the dominant secondary structures within the polypeptide segements, which facilitated a heat-induced sol–to-gel transition, resulting from the supramolecular assembly of β-sheets into nanofibrils. Deconstruction of the three–dimensional networks by mechanical force (sonication) triggered the reverse gel–to–sol transition. Certain enzymes could accelerate the breakdown of the hydrogel, as determined by in vitro gel weight loss profiles. The hydrogels were able to encapsulate and release Npx over 6 days, demonstrating the potential application of these polypeptide hydrogels as an injectable local delivery system for small molecule drugs.