Paclitaxel-loaded micelles composed of folate-poly(ethylene glycol) and poly(γ-benzyl L-glutamate) diblock copolymer

In this study folate-poly(ethylene glycol) and poly(gamma-benzyl L-glutamate) diblock copolymer (FEG) was synthesized and the FEG chemical structure was characterized by H-1 nuclear magnetic resonance (NMR) and Fourier transformation infrared (FTIR). Paclitaxel (PTX)-loaded FEG micelles were self-assembled and the properties of the FEG micelles were evaluated by fluorescence spectroscopy, scanning electron microscope (SEM), transmission electron microscope (TEM), dynamic light scattering (DLS), and in vitro drug-release experiments. It was found that folate groups of the FEG micelles were exposed on the micellar surface, while hydrophobic PTX was successfully entrapped in the core of the micelles to enhance aqueous solubility. The PTX was sustained-released from the FEG micelles depending on the molecular weight of FEG and the pH value of media. The cytotoxicity of blank FEG micelles was low even at high concentration. Through the analysis of fluorescence microscopy and flow cytometry, it indicated that the FITC-labeled FEG micelles were selectively transported to the folate receptor FR(+) HepG-2 cells, but not the FR(-) A549 cells. The free folate in culture media significantly reduced both the uptake of the FITC-labeled FEG micelles by the FR(+) HepG-2 cells and the cytotoxicity of the PTX-loaded FEG micelles against the FR(+) HepG-2 cells. The results suggest that FEG micelles could be transported into FR(+) HepG-2 cells by a FR-mediated endocytosis. FEG micelles will be a promising carrier for targeted delivery of hydrophobic anticancer drug, such as PTX. (C) 2009 Elsevier B.V. All rights reserved.