Treatment of murine SCC VII tumors with localized hyperthermia and temperature-sensitive liposomes containing cisplatin.
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 degrees C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42 degrees 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 degrees 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.
Nishimura
Y
Y
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Ono
K
K
Hiraoka
M
M
Masunaga
S
S
Jo
S
S
Shibamoto
Y
Y
Sasai
K
K
Abe
M
M
Iga
K
K
Ogawa
Y
Y
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D004337:Drug Carriers; D006979:Hyperthermia, Induced; D008081:Liposomes; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000628:therapy*
D004337:Drug Carriers; D008081:Liposomes; D002945:Cisplatin