Liver Cell-Selective Targeting Using Glycosylated Liposomes

Abstract

To develop liver cell-specific liposomal drug carrier systems, we synthesized novel glycosylated cholesterol derivatives, cholesten-5-yloxy-N-(4-((l-imino-2-β-D-thioglycosylethyl)amino)alkyl) formamide. These glycosylated cholesterols were incorporated into liposomes consisting of DSPC and cholesterol. Mean particle size of all prepared liposomes were about 90 nm. After intravenous injection, these glycosylated liposomes were rapidly taken up by the liver. Fractionation of liver cells revealed that galactosyalted liposomes were taken up mainly by liver parenchymal cells while mannosyalted liposomes by liver non-parenchymal cells. Inhibition studies with galactosylated and mannosylated bovine serum albumin suggested that galactosylated and mannosylated liposomes might be recognized by asialoglycoprotein receptor and mannose receptor, respectively. Then, we studied in vivo distribution of prostaglandin E1 (PGE1) and probucol associated with galactosylated liposomes. Liver accumulation of these drugs were significantly higher than that of non-modified liposomes and drug itself. Moreover, PGE1 associated with galactosylated liposomes was effective for acute hepatitis induced by intraperitoneal injection of carbon tetrachloride.