Zou Y Y, Gu X Q, Ueno M, Horikoshi I
Pharmaceutical Research Institute, Shenyang College of Pharmacy.
Yao Xue Xue Bao. 1991;26(9):705-9.
Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 degrees C and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The 14C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery-injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W256 carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and iv injected liposome group.
将温度敏感脂质体包裹的阿霉素注入接种了肝肿瘤的Wistar大鼠的肝动脉。注射两小时后,使用局部热疗将肝脏加热至42摄氏度并维持该温度6分钟。研究了循环中脂质体药物浓度模式的变化以及药物在组织中的分布。结果表明,加热后30分钟,阿霉素从脂质体中释放出来,药物浓度在循环中达到峰值。热疗后,肝脏中的药物总量减少,而肿瘤和尿液中的药物总量增加。14C标记的脂质体追踪试验表明,肝脏注射后8小时内脂质与药物之间保持平行关系,生理环境是脂质体载体变化和存在的决定因素。然而,包裹在脂质体中的药物可以通过热疗来靶向肿瘤。治疗实验表明,与水剂型给药组和静脉注射脂质体组相比,肝动脉注射脂质体加局部热疗组在接种W256癌肉瘤7天后给药的大鼠,其肝肿瘤生长明显受到抑制,动物寿命大大延长。