title: 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.
  
  
  CONCLUSIONS
  This study suggests that Poloxamer 407/TPGS mixed micelles might be a suitable nanocarrier for curcumin to treat multidrug resistant ovarian cancer.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, 1010 West Avenue B, Kingsville, TX 78363, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Saxena
authors.forename: Muhammad Delwar
authors.initials: MD
authors.lastname: Hussain
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D016896:Treatment Outcome; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008823:Micelles; D053769:Nanocapsules; D020442:Poloxamer; D014810:Vitamin E; D011092:Polyethylene Glycols; D003474:Curcumin; C014225:tocophersolan