Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously.

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 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.

• Authors: Xinru Li, Pingzhu Li, Yanhui Zhang, Yanxia Zhou, Xingwei Chen, Yanqing Huang, Yan Liu
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 8 Pg. 1498-511 (Aug 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 20411408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Micelles
• Polyesters
• methoxy poly(ethylene glycol)-poly(lactide)
• pluronic L61
• Poloxamer
• Polyethylene Glycols
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Drug Compounding
• Drug Delivery Systems
• Drug Resistance, Neoplasm
• Female
• Humans
• Inhibitory Concentration 50
• Micelles
• Paclitaxel (administration & dosage)
• Particle Size
• Poloxamer (pharmacokinetics)
• Polyesters (pharmacokinetics)
• Polyethylene Glycols (pharmacokinetics)
• Rats
• Rats, Sprague-Dawley