Redox/ultrasound dual stimuli-responsive nanogel for precisely controllable drug release

Abstract

Ultrasound is expected to be utilized in stimuli-responsive drug delivery systems (DDS) since it is safe, non-invasive and easy to control. In this study, a novel nanogel system with a redox/ultrasound dual stimuli-response has been developed for precise control of drug release. First, a thermo-sensitive copolymer PEI_m–PNIPAM_n–PEI_m self-assembled into micelles in aqueous solution above its LCST. Then, PEI gel shell was formed by using a disulfide-containing cross-linker and spherical nanogels were obtained. Perfluorohexane (PFH) was introduced into the nanogels to provide a cavitation effect under an ultrasound stimulus. Furthermore, the PEI gel shell was specifically disintegrated by glutathione (GSH). The effects of redox/ultrasound on the structure and drug release of the nanogels were investigated. The release rate was found to be accelerated by the above-mentioned factors and a complete release was realized almost instantly. The release mechanism of the nanogels was then investigated. The dual stimuli-responsive nanogels present a promising application prospect for precisely controllable drug delivery/release.