mPEG-b-PCL/TPGS mixed micelles for delivery of resveratrol in overcoming resistant breast cancer

Abstract

Objective: Drug resistance remains a major challenge for effective breast cancer chemotherapy. Resveratrol (Res) is a promising candidate for overcoming cancer chemoresistance, but it has low bioavailability due to poor absorption, and ready metabolism limits its application. This study aims to develop a Res-loaded mixed micelle system to be effective on drug resistance of breast cancer cells.

Methods: A mixed micelle system made of methoxy poly (ethylene glycol)-b-polycaprolactone (mPEG-PCL) and d-α-Tocopherol polyethylene glycol succinate was prepared and Res was encapsulated to form Res-loaded mixed micelles. Furthermore, the antitumor activity against doxorubicin (Dox)-resistant breast cancer MCF-7/ADR cells was studied and the possible mechanism was elucidated.

Results: The mixed micellar formulation increased drug uptake efficiency of Res by Dox-resistant breast cancer MCF-7/ADR cells, and induced higher rates of apoptotic cell death, as assessed by the accumulation of Sub G1 phases of cell cycle, nucleus staining and Annexin-FITC/propidium iodide assay. Moreover, Res-loaded mixed micelles also markedly enhanced Dox-induced cytotoxicity in MCF-7/ADR cells and increased the cellular accumulation of Dox by downregulating the expression of P-glycoprotein (P-gp) and inhibiting the activity thereof.

Conclusion: The cumulative evidence indicates that Res-loaded mixed micelles hold significant promise for the treatment of drug-resistant breast cancer.

Keywords:

• breast cancer resistance
• mixed micelles
• mPEG-b-PCL
• resveratrol
• Tocopherol polyethylene glycol succinate

Declaration of interest

This study was supported by the Macao Science and Technology Development Fund (077/2011/A3) and the Research Fund of the University of Macau (MYRG2014-00033-ICMS-QRCM, MRG012/WYT/2013/ICMS, MYRG 208 (Y3-L4)-ICMS11-WYT). This project was also funded by grant number P20GM104931 from the National Institute of General Medical Sciences (NIGMS), a component of NIH, as well as the Pii Center for Pharmaceutical Technology. The authors declare no other conflicts of interest.

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