Novel Mixed Polymeric Micelles for Enhancing Delivery of Anticancer Drug and Overcoming Multidrug Resistance in Tumor Cell Lines Simultaneously

Pharmaceutical research(2010)

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摘要
BSTRACT Purpose To evaluate novel mixed polymeric micelles based on monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) (mPEG-PLA) and Pluronic L61 for delivery of paclitaxel (PTX) to circumvent unfavorable effects resulting from Cremophore EL in Cremophore EL-based PTX formulation and overcoming multidrug resistance (MDR) in tumor cells at the same time. Methods PTX-loaded plain micelles and mixed micelles were prepared and characterized by determining PTX release in vitro , MDR reversal effect in human breast cancer MDR MCF-7/ADR cell sublines and pharmacokinetics in vivo . Results Both PTX-loaded plain micelles and mixed micelles had similar in vitro release profile. Mixed micellar PTX significantly reduced IC 50 of PTX in MCF-7/ADR cells compared to free PTX and plain micellar PTX, and mixed micelles substantially enhanced cellular accumulation of R 123 in MCF-7/ADR cells compared to free R123 and plain micelles. PTX-loaded mixed micelles with lower content of L61 exhibited comparable cytotoxicity to that observed with Cremophore EL-based PTX formulation in inhibiting the growth of MCF-7/ADR cells. Moreover, plain micelles and mixed micelles retained the pharmacokinetic characteristics of PTX in rats compared with Cremophore EL-based PTX formulation. Conclusion This study suggested that the mixed micelles could enhance delivery of PTX and cell-killing effect for MDR MCF-7/ADR cells.
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关键词
l-lactic acid mpeg-pla.mixed polymeric micelles.multidrug resistance mdr.paclitaxel.pluronic l61,methoxy polyethylene glycol-polyd,multidrug resistance,breast cancer
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