Biodegradable pH/temperature-sensitive oligo(β-amino ester urethane) hydrogels for controlled release of doxorubicin

An injectable biodegradable pH/temperature-sensitive oligo(β-amino ester urethane) (OAEU) was synthesized. The OAEU was synthesized by addition polymerization between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of a synthesized monomer piperazine dihydroxyl amino ester (monomer PDE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized OAEU was characterized by 1H NMR spectroscopy, Fourier transform infrared spectroscopy and gel permeation chromatography. The aqueous solutions of OAEU showed a sol-to-gel-to-sol phase transition as a function of temperature and pH. The gel window covered the physiological conditions (37 °C, pH 7.4) and could be controlled by changing the OAEU concentration. After a subcutaneous injection of the OAEU solution into Sprague–Dawley rats, a gel formed rapidly in situ and remained in the body for more than 2 weeks. The in vitro cytotoxicity test and in vitro degradation showed that the OAEU hydrogel was non-cytotoxic and biodegradable. The in vitro release of doxorubicin from this OAEU hydrogel was sustained for more than 10 days. This injectable biodegradable pH/temperature-sensitive OAEU hydrogel is a potential candidate as a drug/protein carrier and in biomedical applications.

Graphical abstractFor in vivo applications, a solution of OAEU at pH 6.6 with low viscosity (from A, 10 Pa s) was injected into the body and a gel formed in situ with high viscosity under physiological conditions (to B, ∼104 Pa s).Figure optionsDownload full-size imageDownload high-quality image (191 K)Download as PowerPoint slide