Amino acid functionalized pH- and temperature-sensitive biodegradable injectable hydrogels: synthesis, physicochemical characterization and in vivo degradation kinetics

Abstract

In recent years, injectable hydrogels that undergo sol-to-gel phase transition in response to the physiological pH- and temperature have attracted increasing attention in therapeutics delivery. In this study, we developed a biodegradable pH- and temperature-sensitive pentablock copolymers by chemical conjugation of L-cysteine oligomer to the backbone of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymers. A series of pentablock copolymers with various chain lengths were prepared by tuning the reaction time and temperature. These copolymers were freely soluble in water at high pH and low temperature; whereas, they could form a stable gel at the physiological condition (pH 7.4, 37 °C). An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel. In addition, an in vivo biodegradation study of the hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site. Overall, our results show that biodegradable pH- and temperature-responsive hydrogel prepared in this study found to be bioresorbable and could be used as a controlled therapeutics delivery vehicle.