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

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.