Selective accumulation and tumoricidal effect of cisplatin suspended in viscous ethyl oleate on hepatic cancers in animals after intraarterial infusion.
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.
Natsume
H
H
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Imamizu
M
M
Sugibayashi
K
K
Shibata
T
T
Miyagawa
A
A
Morimoto
Y
Y
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D009829:Oleic Acids; D010984:Platinum / Q000493:pharmacokinetics; D051381:Rats; D013535:Suspensions; D014407:Tumor Cells, Cultured; D014783:Viscosity
D009829:Oleic Acids; D013535:Suspensions; D010984:Platinum; D002945:Cisplatin; C033180:ethyl oleate