Anti-Cancer, Pharmacokinetic and Biodistribution Studies of Cremophor EL Free Alternative Paclitaxel Formulation
Subheet K. Jain, Puneet Utreja, Ashok K. Tiwary, Mohit Mahajan, Nikhil Kumar and Partha Roy
Affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005, India.
Keywords: Alternative paclitaxel formulation, anti-cancer activity, biodistribution study, fluorescence microscopy,
intracellular uptake, pharmacokinetic study.
Purpose: The aim of the present investigation is to determine the in vivo potential of previously developed and
optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant
sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed
paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer
activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX
formulation in comparison to marketed paclitaxel formulation.
Methods: Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay
(FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites
carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies.
Results: FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1%
intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation
(85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be
significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and
biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time
(MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation
which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo
performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of
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