Preparation of biodegradable PEGylated pH/reduction dual-stimuli responsive nanohydrogels for controlled release of an anti-cancer drug

Abstract

A facile and efficient method was developed to prepare the monodisperse biodegradable PEGylated pH and reduction dual-stimuli sensitive poly[methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate-co-N,N-bis(acryloyl)cystamine] (PMPB) nanohydrogels with dried particle size below 200 nm via one-step distillation precipitation polymerization as a drug delivery system (DDS) for the controlled release of a wide-spectrum anti-cancer drug, doxorubicin hydrochloride (DOX). Under normal physiological media, the nanohydrogels possessed high drug encapsulation efficiency (more than 96%) within 48 h and exhibited good stability with a trifle premature drug release. However, rapid DOX release was achieved at lower pH or in the presence of reductive reagent glutathione (GSH) with a cumulative release of more than 85% within 30 h. Furthermore, the nanohydrogels manifested nontoxicity on HepG2 cells at a concentration of 10 μg mL⁻¹ or lower. Based on the excellent characteristics of the nanohydrogels, such as low toxicity, impressive biodegradability, sharp dual responsiveness, adequate drug loading capacity and a high drug encapsulation efficiency, they were supposed to have potential application in the area of cancer therapy.