Pharmacokinetics and biodisposition of fluorescein-labeled arabinogalactan in rats.

Fluorescein-labeled arabinogalactan (FA) was prepared by the reaction with FITC in methyl sulphoxide according to the method of deBelder and Granath. A systemic kinetic analysis of FA in rats was carried out by using a specific high-performance size-exclusion chromatography. Intravenously administered FA was rapidly eliminated from the blood circulation followed by an appreciable distribution to the liver and kidney. FA was accumulated in these organs over a long period whereas negligible levels of FA were detected in the other organs. A marked dose-dependency was seen in the hepatic uptake of FA which was markedly reduced by coinjected asialofetuin whereas the renal uptake of FA was not altered. Measurement of the hepatocellular localization demonstrated the overwhelming distribution of FA in the parenchymal liver cell fraction. Furthermore, the microscopic examination revealed FA that was effectively endocytosed by the parenchymal liver cells. These results suggested that FA which is bound to the asialoglycoprotein receptor with a high affinity is subsequently internalized to the hepatocyte via receptor-mediated endocytosis. FA was partially activated by periodate oxidation in order to acquire aldehyde groups to which guest molecules can be bound. A 12.5% oxidized arabinogalactan keeping a hepatocellular targetability showed a good conjugating reactivity to guest molecules via Schiff-base formation or by reductive amination. It was suggested that arabinogalactan can serve as a potential carrier for the delivery of enzymes and drugs to the parenchymal liver cells via the asialoglycoprotein receptor.