http://repository.iitr.ac.in/handle/123456789/1538
Title: | Anti-cancer, pharmacokinetic and biodistribution studies of cremophor EL free alternative paclitaxel formulation |
Authors: | Jain S.K. Utreja P. Tiwary A.K. Mahajan M. Kumar N. Roy, Partha |
Published in: | Current Drug Safety |
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. © 2014 Bentham Science Publishers. |
Citation: | Current Drug Safety (2014), 9(2): 145-155 |
URI: | https://doi.org/10.2174/1574886308666131223123218 http://repository.iitr.ac.in/handle/123456789/1538 |
Issue Date: | 2014 |
Publisher: | Bentham Science Publishers |
Keywords: | Alternative paclitaxel formulation Anti-cancer activity Biodistribution study Fluorescence microscopy Intracellular uptake Pharmacokinetic study |
ISSN: | 15748863 |
Author Scopus IDs: | 55712554200 26536851600 7004094730 55649961700 57192281884 35509207200 |
Author Affiliations: | Jain, S.K., Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India Utreja, P., Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India Tiwary, A.K., Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India Mahajan, M., Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India Kumar, N., Department of Biotechnology, IIT, Roorkee, India Roy, P., Department of Biotechnology, IIT, Roorkee, India |
Corresponding Author: | Jain, S. K.; Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005, India; email: subheetjain@rediffmail.com |
Appears in Collections: | Journal Publications [BT] |
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