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

Org Biomol Chem 2017 Jun 2;15(24):5145-5154. Epub 2017 Jun 2.

Departments of Chemistry, Chemical Engineering, Materials Science and Engineering, and Laboratory for Synthetic-Biologic Interactions, Taxes A&M University, P.O. BOX 30012, 3255 TAMU, College Station, TX 77842, USA.

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.

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Source
http://dx.doi.org/10.1039/c7ob00931cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551480PMC
June 2017

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