Disulfide-crosslinked heparin-pluronic nanogels as a redox-sensitive nanocarrier for intracellular protein delivery

Abstract

Improving the efficacy of drug delivery via nanocarriers has been a major issue in the field of intravenous delivery. In this study, a polymeric nanogel was developed to enhance the stability, redox responsiveness, and the efficacy for intracellular protein delivery. The thiolated heparin-Pluronic conjugate was self-assembled and oxidized to form a disulfide-crosslinked nanogel network under a diluted aqueous condition. The disulfide-crosslinked heparin-Pluronic (DHP) nanogels with encapsulated RNase A were characterized by in vitro release and cytotoxicity tests depending on the existence of glutathione (GSH). The DHP nanogels exhibited reduced hydrodynamic size, higher encapsulation degree, and augmentable release responding to the GSH concentration. The ctotoxicity data confirmed that DHP nanogels were more effective for the intracellular delivery of RNase A compared to non-crosslinked nanogel.