Evaluation of biosafety and intracellular uptake of Cremophor EL free paclitaxel elastic liposomal formulation

Abstract

The present study examines the acute, sub-acute toxicity, and cytotoxicity of paclitaxel elastic liposomal formulation in comparison to a marketed Cremophor EL (polyoxyethylated castor oil):ethanol (1:1, v/v) based formulation. In the previous study, Cremophor EL free paclitaxel elastic liposomal formulation was developed and characterized. Cytotoxicity of formulation was evaluated by MTT assay using A549 cell lines. Percentage intracellular uptake of paclitaxel elastic liposomal and marketed formulation was determined using a fluorescence activating cell sorting assay (FACS) and fluorescence microscopy techniques. Single and repeated dose toxicity measurement showed no mortality, hematological, biochemical, or histopathological changes up to a dose of 120mg/kg for paclitaxel elastic liposomal formulation, in comparison the marketed formulation showed toxicity at a dose of 40mg/kg. Maximum tolerated dose (MTD) for paclitaxel elastic liposomal and marketed formulation was found to be 160mg/kg and 40mg/kg, respectively. Results of FACS analysis showed a 94.6±2.5% intracellular uptake of fluorescence marker acridine orange (AO) loaded in elastic liposomes; in comparison the AO solution showed only a 19.8±1.1% uptake. Paclitaxel elastic liposomal formulation seems to be a better alternative for safe and effective delivery of paclitaxel. This study proves the safety and higher intracellular uptake of paclitaxel elastic liposomal formulation. © 2012 Informa Healthcare USA, Inc.