Fmoc-Conjugated PEG-Vitamin E Micelles for Tumor-Targeted Delivery of Paclitaxel: Enhanced Drug-Carrier Interaction and Loading Capacity.

The purpose of this study is to develop an improved drug delivery system for enhanced paclitaxel (PTX) loading capacity and formulation stability based on PEG-(vitamin E) (PEG-VE) system. PEG-(fluorenylmethoxycarbonyl)-(vitamin E) (PEG-FVE) was synthesized using lysine as the scaffold. PTX-loaded PEG-FVE 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 PEG-FVE micelles have a low CMC value of 4 μg/mL and small sizes (~60 nm). The PTX loading capacity of PEG-FVE micelles was much higher than that of PEG-VE micelles. The Fmoc/PTX physical interaction was clearly demonstrated by a fluorescence quenching assay. PTX-loaded PEG-FVE micelles exerted more potent cytotoxicity than free PTX or Taxol formulation in vitro. Finally, intravenous injection of PTX-loaded PEG-FVE micelles showed superior anticancer activity compared with PEG-VE formulation with minimal toxicity in a mouse model of breast cancer. In summary, incorporation of a drug-interactive motif (Fmoc) into PEG-VE micelles represents an effective strategy to improve the micelle formulation for the delivery of PTX. [ABSTRACT FROM AUTHOR]