Controlling the degradation of pH/temperature-sensitive injectable hydrogels based on poly(β-amino ester)

Abstract

Poly (ethylene glycol) (PEG) — poly(e-caprolactone(CL)-co-D,L-lactide (LA)) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form a temperature sensitive hydrogel triblock copolymer. Poly(β-amino ester) (PAE) obtained from 1,4-butanediol diacrylate (BDA), and 4,4′-trimethylene dipiperidine (TMDP) was used as a pH sensitive moiety to conjugate to the triblock copolymer. The physicochemical properties of the temperature-sensitive triblock and pH/temperature-sensitive pentablock copolymers (PAE-PCLA-PEG-PCLA-PAE) were characterized by 1H NMR spectroscopy and gel permeation spectroscopy. The sol-gel phase transition behavior of the PAE-PCLA-PEG-PCLA-PAE block copolymers was investigated. An aqueous solution of the copolymers (20 wt%) changed from a sol phase at pH 6.4 and 10°C to a gel phase at pH 7.4 and 37°C. In addition, the degradation of PAE-PCLA-PEG-PCLA-PAE was compared with that of poly(ethylene glycol) — poly(e-caprolactone) — poly (β-amino ester) (PAE-PCL-PEG-PCL-PAE) using both in vitro and in vivo experiments. The relationship between the insulin release profile from the matrix and the degradation of these materials also investigated.