Core cross-linked micelles pH-responsive intracellular drug delivery

Cancer is one of the most common causes of mortality in the world over the past decades. There are several therapies for treating cancer that chemotherapy is the most commonly used treatment with anticancer drugs [1]. Most anticancer agents are not as effective in cancer chemotherapy as anticipated because of nonspecific toxicity, lack of tumor selectivity, and development of multidrug resistance (MDR) in various tumors. Various carrier systems such as liposomes, polymeric micelles, nano-scaled complexes and microspheres have been investigated to challenge such problems. In particular, polymeric micelles have become attractive because of their small size (10 to 200 nm) for passive accumulation in solid tumors by a process termed ‘enhanced permeation and retention’ (EPR), improved stability and biodegradability in vivo [2]. In this study, a kind of core cross-linked poly(ethylene glycol)-b-glycidyl azide polymer micelles (PEG-b-GAP) was prepared by a simple chemical cross-linking method for pH-response drug delivery. Curcumin (CU) was then loaded into the micelles in high efficiency [3,4]. The curcumin loaded amphiphilic block copolymer was self-assembled in phosphate buffer (pH 7.4, 0.1 M) into nanosized spherical micelles. In vitro release studies demonstrated that the micelles are relatively stable at normal physiologic conditions but susceptible to tumor relevant reductive and acidic conditions which would trigger the release of chemically loaded drugs. These results suggest that curcumin loaded micelles may offer a promising strategy for CU delivery in the treatment of various tumors, with enhanced efficacy and fewer adverse effects.