Preparation and characterization of highly pH-sensitive biodegradable poly(ether-ester-urethane) and its potential application for drug delivery

Abstract

The objective of this study is to offer a highly pH-sensitive biodegradable polyurethane for application as an intelligent drug delivery carrier. A new pyridinyl diol ((3-((2-(pyridin-4-yl)ethyl)thio) propane-1,2-diol, PyDH) was first synthesized via thiol-ene “click” reaction. Then, PyDH-based poly(ether-ester-urethane) (PEEU-Py) was designed and prepared through the condensation polymerization of PyDH diol, poly(ether-ester) diol and diisocyanate. The pendent pyridine groups and the polyester segments could endow the polymers with pH sensitivity and degradability, respectively. The bulk structures and physicochemical properties of PEEU-Py were characterized via1H NMR, FT-IR, GPC, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and tensile testing. The cast membranes exhibited a sharp transition of the equilibrium swelling ratio (ESR) at pH 8.5∼9.0, and ESR increases of more than twofold and eightfold at pH 1.5 relative to pH 7.4 and pH 12.0, respectively. In vitro drug release studies showed that the release efficiency from the membranes was increased with decreasing pH value. The pH-sensitive release behaviors were related mainly to the swelling ability, and the slow hydrolytic degradation rate of PEEU-Py membranes had minimal influence on it. In addition, the in vitro cytotoxicity was evaluated by an MTT assay with L929 fibroblasts, and a cell viability of more than 75 % indicated satisfactory cytocompatibility. All the results demonstrate the potential application of PEEU-Py as a biological on–off switch for drug carriers that is triggered by an external pH change.