PH-responsive polymer micelles for methotrexate delivery at tumor microenvironments

Abstract

Methotrexate (MTX) anticancer drug was successfully loaded and released in a controlled mannerfrom polymer micelles made of a diblock copolymer of poly(monomethoxy ethylene glycol)-b-poly(ϵ-caprolactone) (mPEG-PCL). The empty and MTX-loaded micelles (MTX/mPEG-PCL) were characterized byelectron microscopy. The drug release dependence upon pH 5.4, 6.5, and 7.4 for 30 days was proven and characterized by UV-Vis spectroscopy. The cytotoxic effect of MTX/mPEG-PCL micelles on MCF-7 breast cancer cells was evaluated through an MTT assay. The morphological analysis indicated the successful formation of micelles of 76 and 131 nm for empty and MTX-loaded micelles, respectively. An encapsulation efficiency of 70.2% and a loading capacity of 8.8% were obtained. The in vitro release of MTX showed a gradual and sustained profile over 22 days, with a clear trend to much higher release at acidic pH (80 and 90% for pH 6.7 and 5.5, respectively). The MTX/mPEG-PCL micelles showed an IC50 of MCF-7 cells at 30 μg mL-1. The results suggested that MTX/mPEG-PCL could be a promising drug delivery system for cancer treatment.