Issue 24, 2017

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

Abstract

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 segments, 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.

Graphical abstract: Multi-responsive polypeptide hydrogels derived from N-carboxyanhydride terpolymerizations for delivery of nonsteroidal anti-inflammatory drugs

Supplementary files

Article information

Article type
Paper
Submitted
14 4月 2017
Accepted
25 5月 2017
First published
02 6月 2017

Org. Biomol. Chem., 2017,15, 5145-5154

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

J. Fan, R. Li, H. Wang, X. He, T. P. Nguyen, R. A. Letteri, J. Zou and K. L. Wooley, Org. Biomol. Chem., 2017, 15, 5145 DOI: 10.1039/C7OB00931C

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