Design and synthesis of novel amphiphilic dendritic galactosides for selective targeting of liposomes to the hepatic asialoglycoprotein receptor

A series of glycolipids have been prepared which contain a cluster galactos ide moiety with high affinity for the hepatic asialoglycoprotein receptor a nd a bile acid eater moiety which mediates stable incorporation into liposo mes. Loading of liposomes with these glycolipids at a ratio of 5% (w/w) res ulted in efficient recognition and uptake of the liposomes by the liver. Pr einjection with asialofetuin almost completely inhibited the uptake, establ ishing that the liposomes were selectively recognized and processed by the asialoglycoprotein receptor on liver parenchymal cells. In contrast, a glyc olipid content of 50% (w/w) led to a liver uptake that could not be inhibit ed by preinjection with asialofetuin, indicating that the liposomes were no w processed by the Gal/Fuc-recognizing receptor on liver macrophages. The r esults presented in this study are important for future targeting of water- soluble and amphiphilic drugs, enveloped in these glycolipid-laden liposome s, to parenchymal liver cells.