A water-soluble cholesteryl-containing trisgalactoside: synthesis, properties, and use in directing lipid-containing particles to the liver

The synthesis of a trisgalactoside-terminated cholesterol derivative is described. Tris(galactosyloxymethyl)-aminomethane is coupled to cholesterol by using glycyl and succinyl as intermediate hydrophilic spacer moieties. The resulting cholesteryl ester dissolves easily in water, forming monodisperse micelles. When added to dispersions of liposomes or plasma lipoproteins in water, the substance becomes incorporated rapidly into these structures, causing an increase of their buoyant density. Liposomes or low-density lipoproteins, preloaded with the substance, are rapidly cleared from the circulation and taken up by the liver after intravenous injection in rats. This uptake is inhibited by N-acetylgalactosamine but not by N-acetylglucosamine, indicating the specificity of this process.