Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: Formulation, optimization and in vitro characterization

The objective of this study was to optimize and characterize a novel polymeric mixed micelle composed of Pluronic P123 and F127 loaded with paclitaxel (M). A Doehlert matrix design was utilized to investigate the effect of four variables, namely P123 mass fraction, amount of water, feeding of M and hydration temperature on the responses including drug-loading coefficient (DL %), encapsulation ratio (ER %) and the percentage of M precipitated from the drug-loaded mixed micelles after 48 h at 37 (PTX precipitated %) for improvement of drug solubilization efficiency and micelle stability. PTX-loaded P123/17127 mixed micelles were prepared by thin-film hydration method. The optimized formulation showed a particle size of about 25 nm with ER % > 90%, and a sustained release behavior compared to Taxol. Micelle formation was confirmed by NMR spectroscopy. The mixed micelles had a low CIVIC of 0.0059% in water. In addition, micelle stability studies implied that introduction of Pluronic F127 (33wt%) into P123 micelle system significantly increased the stability of M-loaded micelles. More importantly, in vitro cytotoxicity was assessed using human lung adenocarcinoma cell lines SPC-A1 and A-549 and was compared to Taxol and the free drug. The cell viability assay against A-549 cells exhibited the 50% inhibition concentration (IC50) of M-loaded P123/17127 mixed micelles (0.1 mu g/ml) was much lower than those of Taxol injection (0.4 mu g/ml) and the free PTX (1.7 mu g/ml). Therefore, M-loaded P123/F127 mixed micelles may be considered as an effective anticancer drug delivery system for cancer chemotherapy. (C) 2009 Elsevier B.V. All rights reserved.