title: Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.
abstract: OBJECTIVE
  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.
authors.forename: Subheet K
authors.initials: SK
authors.lastname: Jain
authors.forename: Puneet
authors.initials: P
authors.lastname: Utreja
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Tiwary
authors.forename: Mohit
authors.initials: M
authors.lastname: Mahajan
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005, India. subheetjain@rediffmail.com.
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol