Pharmacokinetics and biodisposition of fluorescein-labeled arabinogalactanin rats

Fluorcscein-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 specif ic high-performance size-exclusion chromatography. Intravenously administer ed FA was rapidly eliminated from the blood circulation followed by an appr eciable distribution to the liver and kidney. FA was accumulated in these o rgans over a long period whereas negligible levels of FA were detected in t he 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 localizati on demonstrated the overwhelming distribution of FA in the parenchymal live r cell fraction. Furthermore, the microscopic examination revealed FA that was effectively endocytosed by the parenchymal liver cells. These results s uggested that FA which is bound to the asialoglycoprotein receptor with a h igh affinity is subsequently internalized to the hepatocyte via receptor-me diated endocytosis. FA was partially activated by periodate oxidation in or der 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 o r by reductive amination. It was suggested that arabinogalactan can serve a s a potential carrier for the delivery of enzymes and drugs to the parenchy mal liver cells via the asialoglycoprotein receptor. (C) 2000 Elsevier Scie nce B.V. All rights reserved.