Journal
EXPERT OPINION ON DRUG DELIVERY
Volume 12, Issue 3, Pages 361-373Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425247.2014.951634
Keywords
breast cancer resistance; mixed micelles; mPEG-b-PCL; resveratrol; Tocopherol polyethylene glycol succinate
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Funding
- Macao Science and Technology Development Fund [077/2011/A3]
- University of Macau [MYRG2014-00033-ICMS-QRCM, MRG012/WYT/2013/ICMS, MYRG 208 (Y3-L4)-ICMS11-WYT]
- National Institute of General Medical Sciences (NIGMS), NIH [P20GM104931]
- Pii Center for Pharmaceutical Technology
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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-alpha-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.
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