A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Lin Mei,Cunxian Song,Yi Zheng,Yan Tian,Zhen Li,Hongli Chen,Dongye Yang,Kexin Liu,Laiqiang Huang,Hongfan Sun,Ge Tian,Yangqing Zhang

doi:10.1007/s11671-009-9431-6

Abstract

Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere®in the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere®(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

Highlights

Cancer remains the leading cause of death worldwide
The cytotoxicity of PCL nanoparticles was higher than commercial TaxotereÒ in the MCF-7 TAX30 cell culture, but the differences were not significant (p [ 0.05)
Nanoparticles could reduce the multidrug resistance (MDR) that characterizes many anticancer drugs, including docetaxel, by a mechanism of internalization of the drug [2], reducing its efflux from cells mediated by the P-glycoprotein [3]

Summary

Introduction

Cancer remains the leading cause of death worldwide. The global incidence and mortality of breast cancer remains high despite extraordinary progress in understanding the molecular mechanisms underlying carcinogenesis, tumor promotion, and the establishment of molecular targeted therapies [1]. Multidrug resistance (MDR) to anticancer agents remains a major barrier to successful cancer treatment. The development of effective therapies overcoming MDR against invasive breast cancer and highly metastatic disease still remains a significant priority. In comparison to conventional cancer treatments, the nanoscale of these particulate systems minimizes the irritant reactions at the injection site. Nanoparticles and their use in drug delivery is a far more effective cancer treatment method than conventional chemotherapy, which is typically limited by the toxicity of drugs to normal tissues, short circulation half-life in plasma, limited aqueous solubility, and nonselectivity restricting therapeutic efficacy [4]

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