Targetting chemotherapy of brain tumor using liposome encapsulated cisplatin and novel cisplatin derivative

研究了包被多糖脂质体、包被1-氨基乙酸普鲁兰脂质体以及新合成的顺铂衍生物4-吡哆酸二胺羟基铂（pypyt）体外和体内抗肿瘤作用，并与顺铂进行了比较。(1)与中性脂质体相比，将标有^<14>C的普鲁兰包被脂质体经动脉内注入植瘤大鼠9L细胞，脑肿瘤对放射性的摄取增加4.5倍，脾脏对放射性的摄取减少。顺铂对9l -胶质瘤细胞的毒性不受普鲁兰包被脂质体的抑制。颈动脉内给予普鲁兰包被脂质体顺铂后，9L胶质瘤模型大鼠的中位生存时间为35.5 d，对照组为20.3 d （P<0.05）。1-氨基乳糖普鲁兰包被脂质体包裹顺铂进入脑肿瘤的铂量约为普鲁兰包被脂质体包裹顺铂的4倍。(2)大鼠麸皮接种9L胶质瘤，选择颈动脉内灌注匹普特和顺铂。与对照动物相比，生存时间有显著改善。在给药后30分钟，脑肿瘤中的铂浓度比顺铂组高2.4倍。这表明Pypt对9L胶质瘤的药物递送效率高于顺铂。

Antitumor effect of polysaccharide-coated liposome, 1-aminolactose pullulan-coated liposome encapsulated cisplatin and a newly synthesized cisplatin derivative, 4-pyridoxate diammine hydroxy platinum (Pypt), against brain tumours in vitro and in vivo were evaluated and compared with cisplatin.(1)When pullulan-coated liposome labeled with ^<14>C was intracarotidly administrated into the 9L cells in planted brain tumour rats, brain tumours uptake of radioactivity increased 4.5 times and spleen uptake decrease compared with the neutral liposome. The cytotoxity of cisplatin against 9L-glioma cell was not inhibited by encapsulation of pullulan-coated liposomes. The median survival times for 9L glioma rat model following intracarotid administration of pullulan-coated liposome encapsulated cisplatin were 35.5 days and 20.3 days for control (P<0.05). The quantity of platinum of 1-aminolactose pullulan-coated liposome encapsulated cisplatin into the brain tumour was about 4 times as great as that of pullulan-coated liposome encapsulated cisplatin.(2)Rat bran was inoculated with 9L glioma, and Pypt and cisplatin were administered as selective intracarotid infusions. A significant improvement in survival time compared with control animals was found. Platinum concentration in the brain tumours, 30 min after administration of Pypt, was 2.4 times significantly higher than with cisplatin. This suggest that drug delivery efficiency to the 9L glioma is greater for Pypt than cisplatin.