Polymeric Mixed Micelles for Delivery of Curcumin to Multidrug Resistant Ovarian Cancer

Abstract

The biggest challenge for the treatment of multidrug resistance cancer is to deliver high concentration of anticancer drugs specifically to cancer cells for longer period of time. Poloxamers and D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein. Mixed micelles prepared from Poloxamer 407 and TPGS may increases the therapeutic efficacy of drug by delivering high concentration of drug inside the cells and inhibition of P-gp. Curcumin (CUR) is a naturally derived novel anticancer agent but poor solubility limited its clinical use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle encapsulating CUR for treatment of multidrug-resistant ovarian cancer. CUR-loaded Poloxamer 407/TPGS mixed micelles were prepared by thin film hydration method and their physicochemical properties were characterized. Cellular uptake and in vitro cytotoxicity of the CUR-loaded Poloxamer 407/TPGS mixed micelles were studied in multidrug-resistant ovarian cancer (NCI/ADR-RES) cells. The diameter of CUR-loaded Poloxamer 407/TPGS mixed micelles was about 21.4 +/- 0.3 nm and a zeta potential of -11.56 +/- 0.7 mV. The encapsulation efficiency of CUR was ranged from 95-86% with drug loading was about 1-9%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that CUR was encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of CUR for more than 9 days. Results from cellular uptake studies indicated that CUR-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of CUR in NCI/ADR-RES cells. Cytotoxicity of CUR-loaded Poloxamer 407/TPGS mixed micelles was found to be 3 folds more than free CUR after 48 of incubations. This study suggests that Poloxamer 407/TPGS mixed micelles might be a suitable nanocarrier for curcumin to treat multidrug resistant ovarian cancer.