Pharmacokinetic analysis of mannose receptor-mediated hepatic targeting of proteins: capacity-limited hepatic uptake and saturable binding in plasma

摘要

Carbohydrate receptor-mediated endocytosis is a highly cell-specific event and can be applied to in vivo targeted delivery of low molecular-weight drugs, biologically active proteins and DNAs. The asialoglycoprotein (ASGP) receptor expressed only in hepatocytes is one of the most widely utilized mechanisms to deliver biologically active compounds to the cells. We have previously examined the pharmacokinetic aspects of the ASGP receptor-mediated hepatic targeting of galactosylated macromolecules in whole animals and in situ perfused liver. Through these studies it has been revealed that the hepatic uptake is capacity-limited, and the uptake clearance is influenced by the degree of galactosylation.