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

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ABSTRACT

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 IC50 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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ACKNOWLEDGEMENTS

We would like to acknowledge the support of this work by the National Development of Significant New Drugs (New Preparation and New Technology, 2009zx09310-001) and the National Basic Research Program of China (973 program, 2009CB930300).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences Peking University, Beijing, 100191, China

    Xinru Li, Pingzhu Li, Yanhui Zhang, Yanxia Zhou, Xingwei Chen & Yan Liu

  2. Pharmaceutical Teaching Experiment Center School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Yanqing Huang

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  1. Xinru Li
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  2. Pingzhu Li
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  3. Yanhui Zhang
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  4. Yanxia Zhou
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  7. Yan Liu
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Correspondence to Yan Liu.

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Xinru Li and Pingzhu Li contributed equally to this work.

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Li, X., Li, P., Zhang, Y. et al. Novel Mixed Polymeric Micelles for Enhancing Delivery of Anticancer Drug and Overcoming Multidrug Resistance in Tumor Cell Lines Simultaneously. Pharm Res 27, 1498–1511 (2010). https://doi.org/10.1007/s11095-010-0147-1

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