Injectable system and its potential application for the delivery of biomolecules by using thermosensitive poly(gamma-glutamic acid)-based physical hydrogel

Abstract

Poly (gamma-glutamic acid) (PGA) is a natural biomaterial with numerous good properties such as non-toxicity, non-immunogenicity, and water holding. So, various forms of PGA-based materials have been developed for bio-applications, including sheet, cross-linked hydrogel, and nanoparticle except injectable hydrogel type. Considering inherent advantages of injectable system, injectable hydrogel based on PGA can broaden the bio-application range of PGA. In this study, a PGA-based injectable hydrogel system was prepared by physically mixing it with a small amount of chitosan with two different water solubility and molecular weight. The prepared hydrogel system showed a thermo-sensitivity through sol-gel transition behavior in the body temperature change. The mechanical properties and in vitro stability could be modulated by varying the ratio of two types of chitosan. In vitro protein (human bFGF) delivery using this injectable formulation showed a sustained release for similar to 2 weeks while preserving its bioactivity. In addition, the in situ formation of this PGA-based hydrogel formulation upon subcutaneous injection was demonstrated in vivo. The hydrogel formed in vivo also showed a long term (similar to 2 weeks) stability without noticeable inflammatory response. Therefore, the present formulation can be applied as a promising injectable hydrogel system for tissue engineering or drug delivery. (C) 2017 Elsevier B.V. All rights reserved.