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Abstract
Background
Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.
Methods
Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.
Results
Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.
Conclusion
This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.
Acknowledgment
This study was financially supported by the Scientific Research Fund of the Ministry of Health-Medical Science Critical Technological Program of Zhejiang Province, China (No. WKJ2008-2-029) the Natural Science Foundation of Zhejiang Province, China (No. Y2110124) and the Research Fund for the Doctoral Program of Higher Education of China (No. 20090101120141).
Disclosure
The authors report no conflicts of interest in this work.