pH- and temperature-sensitive PCL-grafted poly(β-amino ester)-poly(ethylene glycol)-poly(β-amino ester) copolymer hydrogels

摘要

A series of poly(ɛ-caprolactone)-grafted poly(β-amino ester)-poly(ethylene glycol)-poly(β-amino ester) ((PAE-g-PCL)-PEG-(PAE-g-PCL)) copolymers were designed and synthesized for use in injectable pH- and temperature-sensitive hydrogels. First, PEG diacrylate was synthesized and used as a macroinitiator, and the chain was extended by 4,4 trimethylene dipiperidine (TMDP), 3-amino-1-propanol and diacrylate monomers (1,4-butanediol diacrylate (BDA), and 1,6-hexanediol diacrylate (HDA)) to obtain the triblock copolymers (PAE-PEG-PAE). Poly (ɛ-caprolactone) was then grafted to the pendant OH groups of the resulting PAE-PEG-PAE by ring opening polymerization. The PAE-PEG-PAE and (PAE-g-PCL)-PEG-(PAE-g-PCL) copolymers were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography. The phase diagram was measured using the tube inverting method. At pH 6.6 or higher, the (PAE-g-PCL)-PEG-(PAE-g-PCL) copolymer solutions (30 wt%) displayed sol-gel-sol transitions with increasing temperature. The viscosity of the graft copolymer solutions was determined as a function of temperature by dynamic mechanical analysis. In addition, after the subcutaneous injection of the polymer solution (30 wt%, pH 6.4) into a rat, a gel formed within a short time, suggesting biomedical applications.