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

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 62; no. 1; pp. 32 - 38
• Main Authors: Wang, Shao-ning, Deng, Yi-hui, Xu, Hui, Wu, Hong-bing, Qiu, Ying-kun, Chen, Da-wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 2006
• Subjects: alpha-Fetoproteins - metabolism; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacokinetics; Asialoglycoproteins - metabolism; Binding, Competitive; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Drug Delivery Systems; Female; Fetuins; Galactosides - chemical synthesis; Galactosylated lipid; Hepatocyte-selective targeting; Hepatocytes - metabolism; Lipids - administration & dosage; Lipids - chemical synthesis; Liposomes; Mice; Parenchymal cells; Particle Size; Liposomes; Parenchymal cells; Galactosylated lipid; Doxorubicin; Hepatocyte-selective targeting
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2005.07.004

This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3 β-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.