Polymeric nanoassemblies entrapping curcumin overcome multidrug resistance in ovarian cancer.

The increasing emergence of multidrug-resistant (MDR) cells presents a challenge to effective cancer therapy. Curcumin (CUR) has multifunctional anticancer properties, but its clinical use has been limited by poor solubility. We developed biodegradable polymeric micelles entrapping CUR in order to improve its antitumor activity and to explore whether it could treat MDR cells. This delivery system produced small micelles with a high encapsulation efficiency, good stability, and slow release of CUR. CUR micelles showed cytotoxic effects in wild-type drug-sensitive A2780s and in paclitaxel-resistant A2780t ovarian adenocarcinoma cells. The concentration of free CUR that reduced cell viability by 50% (IC 50 ) was 1.5 fold and 1.2 fold higher than that of CUR micelles in A2780s and A2780t cells, respectively. Cellular uptake studies indicated that delivery by micelles improved CUR uptake into both cell lines. Cell cycle analysis suggested that CUR micelles induced apoptosis and enhanced G2/M arrest. Overall, CUR micelles may provide a novel strategy to improve the clinical management of MDR ovarian cancer. [ABSTRACT FROM AUTHOR]