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Current Drug Safety
ISSN (Print): 1574-8863
ISSN (Online): 1574-8863
Epub Abstract Ahead of Print
DOI: 10.2174/1574886308666131223123218      Price:  $95









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

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Author(s): Subheet Kumar Jain, Puneet Utreja, A.K. Tiwary, Mohit Mahajan, Nikhil Kumar and Partha Roy
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Abstract:
Purpose: The aim of 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 present examination, intracellular uptake, repeat 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 activating 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 significant increase was observed in 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 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 result of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears promising carrier for sustained and targeted delivery of paclitaxel
Affiliation:
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005 INDIA