Sustained delivery of doxorubicin using biodegradable pH/temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) multiblock copolymer hydrogels

Abstract

Polymers containing amino urethane groups have great potential as polymeric hydrogel carriers for the delivery of drugs/proteins because of their non-toxicity and ability to form hydrogen bonds and ionic interactions with biomolecules. However, the reported gels have high molecular weights and/or are non-biodegradable or showed fast degradation. This study examined a series of low molecular weight, biodegradable pH/temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) and their potential appication for drug sustained release. The copolymers were synthesized and characterized by ¹H and ¹³C NMR, Fourier transform infrared spectroscopy and gel permeation chromatography. Aqueous solutions of the copolymer showed a gel-to-sol phase transition as a function of temperature in the pH range of 6.8–7.6. The gel window covered the physiological conditions (37 °C, pH 7.4). The gel region could be controlled by changing PEG/PAEU ratio, copolymer solution concentration and PEG molecular weight. A gel formed rapidly in situ after injecting the copolymer solution subcutaneously into SD rats. The non-cytotoxicity of this hydrogel was confirmed by in vitro cytotoxicity test and the in vitro release of doxorubicin from this hydrogel was sustained for more than 5 weeks. This novel injectable biodegradable pH/temperature-sensitive hydrogels can be a potential candidate for drugs carrier.