Nishimura Y, Ono K, Hiraoka M, Masunaga S, Jo S, Shibamoto Y, Sasai K, Abe M, Iga K, Ogawa Y
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Radiat Res. 1990 May;122(2):161-7.
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.
研究了通过局部热疗将包裹在温度敏感单层脂质体中的顺铂（CDDP）释放到小鼠SCC VII癌中，以及该治疗对肿瘤生长的影响。含顺铂的温度敏感脂质体（LIP-CDDP）的转变温度为41℃。注射LIP-CDDP 24小时后，加热的肿瘤（42℃，60分钟）所含的CDDP比接受游离CDDP的未加热肿瘤多3.3倍。虽然注射后1.5小时肝脏对脂质体相关CDDP的摄取量比游离CDDP的摄取量大约高三倍，但在24小时内它下降了约50%。未观察到两种形式的CDDP在肾脏摄取上的差异。相对于CDDP的量，LIP-CDDP与42或43℃的局部加热相结合在延迟肿瘤生长方面比游离CDDP和热疗更有效。与游离CDDP且无热疗相比，LIP-CDDP加局部加热治疗产生的剂量修正因子为5.3。当将LIP-CDDP与热疗的治疗与游离CDDP与热疗的治疗进行比较时，剂量修正因子为2.8。因此，CDDP可通过加热从温度敏感脂质体中选择性释放，从而导致药物摄取量增加和肿瘤生长延迟。
