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 3-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 PTXloaded 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 noncross- 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 crosslinked PMAA-b-PFM micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to tumors.