Treatment of Murine SCC VII Tumors with Localized Hyperthermia and Temperature-Sensitive Liposomes Containing Cisplatin

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Abstract
The release of cisplatin (CDDP) encapsulated in temperature-sensitive unilamellar liposomes to murine SCC VII carcinoma by localized hyperthermia and the effects of the treatment on tumor growth were studied. A transition temperature of the temperature-sensitive liposomes containing cisplatin (LIP-CDDP) was 41.degree. C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42.degree. C, 60 min) contained 3.3 times more CDDP than the unheated tumors receiving free CDDP. Although the uptake of liposome-associated CDDP by liver was approximately threefold greater at 1.5 h after injection than uptake of free CDDP, it decreased about 50% over a 24-h period. No difference in uptake of the two forms of CDDP by kidney was observed. The combination of LIP-CDDP and localized heating at 42 or 43.degree. C was more effective relative to the amount of CDDP in delaying tumor growth than that of free CDDP and hyperthermia. Treatment with LIP-CDDP plus local heating resulted in a dose-modifying factor of 5.3 when compared with free CDDP and no hyperthermia. The dose-modifying factor was 2.8 when treatment with LIP-CDDP and heat was compared with treatment with free CDDP and heat. Thus CDDP could be released selectively from the temperature-sensitive liposomes by heat and resulted in both a greater uptake of the drug and a delay in tumor growth.

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