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Pharmaceutical Research

, Volume 27, Issue 8, pp 1498–1511 | Cite as

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

  • Xinru Li
  • Pingzhu Li
  • Yanhui Zhang
  • Yanxia Zhou
  • Xingwei Chen
  • Yanqing Huang
  • Yan Liu
Research Paper

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.

KEY WORDS

methoxy poly(ethylene glycol)-poly(D,L-lactic acid) (mPEG-PLA) mixed polymeric micelles multidrug resistance (MDR) paclitaxel pluronic L61 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Xinru Li
    • 1
  • Pingzhu Li
    • 1
  • Yanhui Zhang
    • 1
  • Yanxia Zhou
    • 1
  • Xingwei Chen
    • 1
  • Yanqing Huang
    • 2
  • Yan Liu
    • 1
  1. 1.Department of PharmaceuticsSchool of Pharmaceutical Sciences Peking UniversityBeijingChina
  2. 2.Pharmaceutical Teaching Experiment Center School of Pharmaceutical SciencesPeking UniversityBeijingChina

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