Anti-Cancer, Pharmacokinetic and Biodistribution Studies of Cremophor EL Free Alternative Paclitaxel Formulation

Title:Anti-Cancer, Pharmacokinetic and Biodistribution Studies of Cremophor EL Free Alternative Paclitaxel Formulation

Volume: 9 Issue: 2

Author(s): Subheet K. Jain, Puneet Utreja, Ashok K. Tiwary, Mohit Mahajan, Nikhil Kumar and Partha Roy

Affiliation:

Keywords: Alternative paclitaxel formulation, anti-cancer activity, biodistribution study, fluorescence microscopy, intracellular uptake, pharmacokinetic study.

Abstract: 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 paclitaxel.

Cite this article as:

Jain K. Subheet, Utreja Puneet, Tiwary K. Ashok, Mahajan Mohit, Kumar Nikhil and Roy Partha, Anti-Cancer, Pharmacokinetic and Biodistribution Studies of Cremophor EL Free Alternative Paclitaxel Formulation, Current Drug Safety 2014; 9 (2) . https://dx.doi.org/10.2174/1574886308666131223123218