Cross-linked micelles of graftlike block copolymer bearing biodegradable ε-caprolactone branches: a novel delivery carrier for paclitaxel

Abstract

The poor stability of micellar drug delivery system in vivo due to large volume dilution often leads to premature drug release with low therapeutic efficacy. In this study, shell cross-linked micelles of graftlike block copolymer bearing biodegradable ε-caprolactone branches (PMAA-b-PFM) were prepared to be used as a novel carrier for paclitaxel (PTX). PTX was successfully encapsulated into the hydrophobic cores of the cross-linked micelles using the dialysis method. The resultant PTX-loaded cross-linked micelles were about 99 nm in diameter with spherical shape and high encapsulation efficiency. The PTX-loaded cross-linked micelles had smaller sizes and better stability as compared to the non-cross-linked controls. Fluorescence microscopy and flow cytometry studies showed that PTX-loaded cross-linked micelles had excellent cellular uptake ability by bone marrow derived macrophages and human glioma U87 cells. Cellular uptake of cross-linked micelles was found to be higher than non-cross-linked controls due to smaller size. In vitro cytotoxicity studies also revealed that the PTX-loaded cross-linked micelles exhibit high anti-cancer activity to U87 cells. These results suggested that cross-linked PMAA-b-PFM micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to tumors.