Targeting of anticancer drugs and genome medicine by utilizing absorption from the liver surface

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Development of drug delivery system to achieve site-specific delivery or prolonged retention in the circulation has attracted attention, because new types of drugs are expected to be created with advance in life science and biotechnology such as human genome project. We have tried to develop a new administration route for drug targeting to the liver, since normal drug administration by intravenous and oral route have difficulty in achieving a local site of action in the liver. As an anticancer model drug 5-fluorouracil (5-FU), we examined its hepatic disposition after application to the rat liver surface by employing a diffusion cell, and indicated the possibility for liver targeting. In addition, we suggested the novel application route to the other organ surfaces for genome medicine. Furthermore, we have examined the influence of liver disease on drug absorption from the liver surface membrane regarded as the first barrier for drug targeting to the liver. The main purpose of this study is to examine the possibility of direct liver surface application for drug targeting method. We employed rats intoxicated with carbon tetrachloride (CC14) or D-galactosamine (GAL) as the liver disease model, and examined drug absorption characteristics after application to the liver surface, by utilizing a cylindrical diffusion cell. In the liver-intoxicated rats, about 90 % of a low molecular weight drug phenolsulfonphthalein (PSP) as a model was absorbed from the liver surface in 6 h, similar to the normal rats (no treatment). Although the absorption rate was increased in the CC14 group whereas slightly retarded absorption was observed in GAL group, there should be no serious problem for clinical use of liver surface application. Consequently, it is expected that no marked decline in the absorption rate from liver surface in liver disease state and liver resection, leading to apply this administration method for liver targeting.