Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

Abstract

PURPOSE:

In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated.

METHODS:

Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay.

RESULTS:

In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation.

CONCLUSION:

The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

• Authors: Puneet Utreja, Subheet Jain, Subodh Yadav, K L Khandhuja, A K Tiwary
• Journal: Current drug safety (Curr Drug Saf) Vol. 6 Issue 5 Pg. 329-38 (Nov 01 2011) ISSN: 2212-3911 [Electronic] United Arab Emirates
• PMID: 22424541 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Excipients
• Liposomes
• Phosphatidylcholines
• Deoxycholic Acid
• cremophor EL
• Paclitaxel
• Glycerol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology, toxicity)
• Carcinoma, Small Cell (drug therapy, pathology)
• Cell Line, Tumor
• Deoxycholic Acid (chemistry)
• Dose-Response Relationship, Drug
• Excipients (chemistry)
• Female
• Glycerol (analogs & derivatives, chemistry)
• Humans
• Lethal Dose 50
• Liposomes
• Lung Neoplasms (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Mice
• Paclitaxel (administration & dosage, pharmacology, toxicity)
• Phosphatidylcholines (chemistry)
• Soybeans (chemistry)