Research paper
Pharmacokinetics of receptor-mediated hepatic uptake of glycosylated albumin in mice

https://doi.org/10.1016/0378-5173(92)90136-PGet rights and content

Abstract

Three types of glycosylated bovine serum albumins (BSA) labeled with 111In were synthesized and their disposition characteristics were studied in mice. At lower doses (0.05–0.1 mg/kg), intravenously injected galactosylated BSA (Gal-BSA) and glucosylated BSA (Glc-BSA) were rapidly eliminated from plasma due to extensive uptake by the liver, and their calculated apparent uptake clearances were fairly close to the hepatic plasma flow and also the total body clearance in each experiment. However, their hepatic uptake was nonlinear and decreased at higher doses. Mannosylated BSA (Man-BSA) also showed preferential hepatic uptake although the maximum rate of uptake was about one quarter of those of Gal-BSA and Glc-BSA. The cellular distribution of Gal-BSA and Man-BSA in the liver was consistent with the localization pattern of receptors recognizing galactose or mannose residues; i.e., preferential accumulation was shown in the parenchymal (Gal-BSA) or non-parenchymal (Man-BSA) cells. The time courses observed for plasma concentration and liver accumulation of glycosylated albumins were satisfactorily described based on a physiological model including hepatic plasma flow. These results suggest a potential and limitation of glycosylated albumins as carriers for hepatic cellular targeting.

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