PMID- 24369111
OWN - NLM
STAT- MEDLINE
DCOM- 20150818
LR  - 20191112
IS  - 2212-3911 (Electronic)
IS  - 1574-8863 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free 
      alternative paclitaxel formulation.
PG  - 145-55
AB  - 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.
FAU - Jain, Subheet K
AU  - Jain SK
FAU - Utreja, Puneet
AU  - Utreja P
FAU - Tiwary, Ashok K
AU  - Tiwary AK
FAU - Mahajan, Mohit
AU  - Mahajan M
FAU - Kumar, Nikhil
AU  - Kumar N
FAU - Roy, Partha
AU  - Roy P
AD  - Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 
      Punjab, 143 005, India. subheetjain@rediffmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Drug Saf
JT  - Current drug safety
JID - 101270895
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 6D4M1DAL6O (cremophor EL)
RN  - P88XT4IS4D (Paclitaxel)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*administration & dosage
MH  - Carcinoma, Ehrlich Tumor/drug therapy
MH  - Chemistry, Pharmaceutical
MH  - Female
MH  - Glycerol/administration & dosage/*analogs & derivatives
MH  - Male
MH  - Mice
MH  - Paclitaxel/*administration & dosage/adverse effects/pharmacokinetics/pharmacology
MH  - Tissue Distribution
EDAT- 2013/12/27 06:00
MHDA- 2015/08/19 06:00
CRDT- 2013/12/27 06:00
PHST- 2013/09/25 00:00 [received]
PHST- 2013/12/10 00:00 [revised]
PHST- 2013/12/13 00:00 [accepted]
PHST- 2013/12/27 06:00 [entrez]
PHST- 2013/12/27 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
AID - CDS-EPUB-58229 [pii]
AID - 10.2174/1574886308666131223123218 [doi]
PST - ppublish
SO  - Curr Drug Saf. 2014;9(2):145-55. doi: 10.2174/1574886308666131223123218.