Abstract
Antitumor effects of ethyl oleate (EO), Lipiodol Ultra-Fluide® (LP) and viscous ethyl oleate (VEO) containing cis-diamminedichloro platinum (II) (CDDP) on the tumor-bearing animals were investigated. The in vitro CDDP release from EO and LP was fast and the total CDDP was released within 24 h. In contrast, CDDP release from VEO was very slow. When these oily drug carriers were infused into the proper artery of the liver implanted with VX-2 tumor in rabbits, the rank order of the accumulation of CDDP in the tumor site was VEO > LP > EO. However, the inhibition effect of these oily drug carriers on the tumor growth was almost the same. Next, controlled drug release property of the VEO was evaluated by addition of non-ionic surfactants (Tween 80, Span 20 and 80) using the AH 272 ascites in rats. The in vitro CDDP release from the VEO containing the surfactants was faster than that without the surfactants (the extent of suppress was Span 80 > Span 20 > Tween 80). The mean survival (T/C%) of EO-, LP-, VEO containing Tween 80, Span 20 or Span 80-treated groups was 164.5, 179.4, 166.7, 298. 6 or 475.4, respectively. These results suggested that VEO containing non-ionic surfactants was very useful as a bifunctional drug carrier with abilities of “targeting” and “controlled release” for intra-arterial infusion therapy.
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