The purpose of this study is to develop an improved drug delivery system for enhanced
paclitaxel (PTX) loading capacity and formulation stability based on PEG5K-(vitamin E)2 (PEG5K-VE2) system. PEG5K-(fluorenylmethoxycarbonyl)-(vitamin E)2 (PEG5K-FVE2) was synthesized using
lysine as the scaffold. PTX-loaded PEG5K-FVE2
micelles were prepared and characterized. Fluorescence intensity of Fmoc in the
micelles was measured as an
indicator of
drug-carrier interaction. Cytotoxicity of the
micelle formulations was tested on various tumor cell lines. The therapeutic efficacy and toxicity of PTX-loaded
micelles were investigated using a syngeneic mouse model of
breast cancer (4T1.2). Our data suggest that the PEG5K-FVE2
micelles have a low CMC value of 4 μg/mL and small sizes (~60 nm). The PTX loading capacity of PEG5K-FVE2
micelles was much higher than that of PEG5K-VE2
micelles. The Fmoc/PTX physical interaction was clearly demonstrated by a fluorescence quenching assay. PTX-loaded PEG5K-FVE2
micelles exerted more potent cytotoxicity than free PTX or
Taxol formulation in vitro. Finally,
intravenous injection of PTX-loaded PEG5K-FVE2
micelles showed superior anticancer activity compared with PEG5K-VE2 formulation with minimal toxicity in a mouse model of
breast cancer. In summary, incorporation of a
drug-interactive motif (Fmoc) into PEG5K-VE2
micelles represents an effective strategy to improve the
micelle formulation for the delivery of PTX.