TITLE

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

AUTHOR(S)
Xinru Li; Pingzhu Li; Yanhui Zhang; Yanxia Zhou; Xingwei Chen; Yanqing Huang; Yan Liu
PUB. DATE
August 2010
SOURCE
Pharmaceutical Research;Aug2010, Vol. 27 Issue 8, p1498
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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. 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. 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. This study suggested that the mixed micelles could enhance delivery of PTX and cell-killing effect for MDR MCF-7/ADR cells.
ACCESSION #
51931182

 

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