Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin

• DOI: 10.1016/j.ejpb.2005.07.004
• Publication Date: 2005-10-15T11:11:00Z
• Authors: S WANG; Y DENG; H XU; H WU; Y QIU; D CHEN
• Keywords: liposomes; 0303 health sciences; Antibiotics, Antineoplastic; 500; Asialoglycoproteins; Galactosides; doxorubicin; Binding, Competitive; Lipids; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; Doxorubicin; galactosytated lipid; Liposomes; Hepatocytes; parenchymal cells; Animals; Female; alpha-Fetoproteins; Particle Size; Fetuins; hepatocyte-selective targeting

This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3beta-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate (CHS-ED-LA), and the targetability of doxorubicin (DOX), a model drug, in liposomes containing 10% mol/mol CHS-ED-LA (galactosylated liposomes, GalL) to the liver was studied. The weighted-average overall drug targeting efficiency (Te(*)) was used to evaluate the liver targetability of GalL DOX. The results showed that GalL DOX gave a relatively high (Te(*))(liver) value of 64.6%, while DOX in conventional liposome (CL DOX) only gave a (Te(*))(liver) value of 21.8%. In the liver, the GalL DOX was mainly taken up by parenchymal cells (88% of the total hepatic uptake). Moreover, preinjection of asialofetuin significantly inhibited the liver uptake of GalL DOX (from 70 to 12% of the total injected dose). It was suggested that liposomes containing such novel galactosylated lipid, CHS-ED-LA, had a great potential as drug delivery carriers for hepatocyte-selective targeting.