Natsume H, Imamizu M, Sugibayashi K, Shibata T, Miyagawa A, Morimoto Y
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
J Drug Target. 1993;1(3):207-15. doi: 10.3109/10611869308996078.
The selective accumulation and tumoricidal effects of cisplatin after intra-arterial infusion suspended in viscous ethyl oleate (VEO) on hepatic cancers of AH 272 tumor-bearing rats and VX-2 tumor-bearing rabbits were compared with those of cisplatin suspensions in ethyl oleate (EO) and Lipiodol Ultra Fluide (LP). The viscosities of VEO, EO and LP were 120, 4, and 21 centipoise (cp) respectively. Complete in vitro release of cisplatin from EO and LP occurred within 24 h, whereas only about 25% of cisplatin was released from VEO over the same period. When EO or VEO containing 3H-oleic acid were infused into the hepatic artery of rat liver inoculated with AH 272 tumor cells, radioactivity in the tumor site was higher than that in normal liver. In the case of cisplatin, concentration ratios after the infusion of EO and VEO were almost the same as those of oily carriers. Similar results were obtained in rabbit liver inoculated with VX-2 tumor cells. Cisplatin concentration in the tumor site seven days after intra-arterial infusion of VEO suspension was 5- and 1.7-fold higher, respectively, than that after EO and LP suspensions. The tumoricidal effect of cisplatin in VEO suspension on AH 272 tumor-bearing rats was higher than that after cisplatin solution and EO and LP suspensions, while VX-2 tumor growth was inhibited by the infusion of all cisplatin-containing oily carriers. VEO suspension thus appears very promising in intra-arterial infusion therapy.
将顺铂悬浮于粘性油酸乙酯(VEO)中经动脉内输注后对AH 272荷瘤大鼠和VX - 2荷瘤兔肝癌的选择性蓄积和杀肿瘤作用,与顺铂悬浮于油酸乙酯(EO)和超液化碘油(LP)中的情况进行了比较。VEO、EO和LP的粘度分别为120、4和21厘泊(cp)。顺铂从EO和LP中的体外完全释放发生在24小时内,而同期顺铂从VEO中的释放量仅约为25%。当将含有3H - 油酸的EO或VEO注入接种了AH 272肿瘤细胞的大鼠肝脏动脉时,肿瘤部位的放射性高于正常肝脏。对于顺铂,输注EO和VEO后的浓度比与油性载体的浓度比几乎相同。在接种VX - 2肿瘤细胞的兔肝脏中也获得了类似结果。动脉内输注VEO混悬液7天后肿瘤部位的顺铂浓度分别比输注EO和LP混悬液后高5倍和1.7倍。顺铂在VEO混悬液中对AH 272荷瘤大鼠的杀肿瘤作用高于顺铂溶液以及EO和LP混悬液,而VX - 2肿瘤的生长受到所有含顺铂油性载体输注的抑制。因此,VEO混悬液在动脉内输注治疗中似乎非常有前景。