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

研究了多糖包衣脂质体、1-氨基乳糖-普鲁兰糖脂质体包裹顺铂和新合成的顺铂衍生物4-吡哆酸二胺-羟基铂(Pypt)在体内外抗脑肿瘤的作用，并与顺铂进行了比较。(1)将标记有~(14)&gt；C的普鲁兰糖脂质体注入9L细胞后，脑瘤细胞对放射性的摄取比中性脂质体高4.5倍，脾摄取比中性脂质体低4.5倍。普鲁兰多糖包被的脂质体不能抑制顺铂对9L-胶质瘤细胞的杀伤作用。9L脑胶质瘤模型大鼠颈动脉注射普鲁兰多糖脂质体包裹顺铂后的中位生存期为35.5天，对照组为20.3天(P&lt；0.05)。1-氨基乳糖-普鲁兰糖脂质体包裹顺铂的载铂量约为普鲁兰-普鲁兰脂质体-顺铂的4倍。(2)大鼠脑内接种9L胶质瘤，Pypt和顺铂选择性注入。与对照动物相比，小鼠的存活时间显著延长。Pypt给药30min后，脑瘤中铂的浓度是顺铂的2.4倍。提示Pypt对9L胶质瘤的药物传递效率高于顺铂。

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.