Thermosensitive liposomal taxol formulation: heat-mediated targeted drug delivery in murine melanoma.
Taxol, an antitumour alkaloid which stabilizes microtubules, demonstrates marked activity against several tumours. However, due to its low aqueous solubility, Cremophor EL (polyoxyethylated castor oil) is used as the excipient in pharmaceutical drug preparations of taxol. This has toxic side effects, thereby limiting the clinical use of taxol in cancer therapy. The aim of this study was to design a novel taxol formulation using thermosensitive liposomes in order to eliminate the Cremophor EL vehicle and improve the antitumour activity of taxol by site-specific drug delivery. Temperature-sensitive liposomes encapsulating taxol were prepared using the natural lipids egg phosphatidylcholine and cholesterol in combination with ethanol. The liposomes have a phase transition temperature (Tm) of 43 degrees C. The in vivo efficacy of thermosensitive liposome encapsulated taxol was determined in B16F10 murine melanoma transplanted into C57BI/6 mice in combination with local hyperthermia. A significant reduction in tumour volume and an increase in survival time was observed in tumour-bearing mice treated with a combination of hyperthermia and thermosensitive liposome encapsulated taxol compared with animals treated with an equivalent dose of free taxol with or without hyperthermia. These results suggest that thermosensitive liposome encapsulated taxol in combination with hyperthermia may be useful in improving the therapeutic efficacy of taxol in the treatment of melanoma.
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
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Sharma
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Chelvi
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Kaur
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Ralhan
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002784:Cholesterol; D003131:Combined Modality Therapy; D004337:Drug Carriers; D000431:Ethanol; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage*; D010713:Phosphatidylcholines; D011897:Random Allocation; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D000431:Ethanol; D002784:Cholesterol; D017239:Paclitaxel