title: 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 120 mg/kg for paclitaxel elastic liposomal formulation, in comparison the marketed formulation showed toxicity at a dose of 40 mg/kg. Maximum tolerated dose (MTD) for paclitaxel elastic liposomal and marketed formulation was found to be 160 mg/kg and 40 mg/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.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Utreja
authors.forename: Subheet
authors.initials: S
authors.lastname: Jain
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwary
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004548:Elasticity; D005260:Female; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000009:adverse effects / Q000378:metabolism*; D014677:Pharmaceutical Vehicles / Q000009:adverse effects; D011897:Random Allocation; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D008081:Liposomes; D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol