Triple-stimuli (pH/thermo/reduction) sensitive copolymers for intracellular drug delivery

The development of novel thermo-, pH- and reduction-sensitive polymeric micelles based on a block copolymer p(PEG-MEMA-co-Boc-Cyst-MMAm-co-VI)-b-PEG (PPBV) for the intracellular delivery of anticancer drugs is reported. The pH/temperature-responsive behaviour of PPBV is observed by both DLS and UV-Vis experiments. The PPBV micelles prepared by a quick heating process are stable in PBS (pH 7.4, 37 °C) for over 48 h and are stable in the presence of serum for at least 12 h. Paclitaxel (PTX) was loaded into the PPBV micelles with a high encapsulation efficiency (>85%), resulting in a high drug loading content (up to 26 wt%) by a simple heating method. The PTX-loaded micelles show slow drug release in PBS and rapid release after exposure to a weakly acidic pH or reductive environment. The PTX-loaded micelles showed higher cytotoxicity against HepG2 cells with increasing PTX concentration, whereas empty micelles are found to be non-toxic. These multi-sensitive polymeric micelles may serve as promising carriers for cytostatic drugs.