Hyperthermia-mediated targeted delivery of thermosensitive liposome-encapsulated melphalan in murine tumors

Targeted drug delivery systems combining thermosensitive liposome-entrapped anticancer drugs and hyperthermia have been tried for targeting drugs to tumors. These heat-sensitive liposomes are prepared from synthetic lipids. Herein we report the use of thermosensitive liposomes composed of natural lipids, viz., egg phosphatidyl choline, cholesterol, and ethanol, having phase transition temperature of 42.7 degrees C for targeted drug delivery. The antitumor effect of melphalan encapsulated in thermosensitive small unilamellar liposomes administered in combination with hyperthermia was studied in C57B1/6 mice bearing B16F10 melanoma. The in vivo efficacy of liposome-encapsulated melphalan in combination with hyperthermia as measured by reduction in tumor volume and increased survival time was greater than that of an equivalent concentration of free melphalan with or without heating. These results suggest that the combination of drug-loaded natural lipid-derived thermosensitive liposomes with local hyperthermia at the tumor site could be useful in enhancing drug delivery to tumors and improving its therapeutic efficacy in treatment of solid tumors.