title: Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin.
abstract: 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.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Shao-Ning
authors.initials: SN
authors.lastname: Wang
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Deng
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Wu
authors.forename: Ying-Kun
authors.initials: YK
authors.lastname: Qiu
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001212:Asialoglycoproteins / Q000378:metabolism; D001667:Binding, Competitive; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D060748:Fetuins; D005697:Galactosides / Q000138:chemical synthesis*; D022781:Hepatocytes / Q000378:metabolism*; D008055:Lipids / Q000008:administration & dosage / Q000138:chemical synthesis*; D008081:Liposomes; D051379:Mice; D010316:Particle Size; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D001212:Asialoglycoproteins; D060748:Fetuins; D005697:Galactosides; D008055:Lipids; D008081:Liposomes; D000509:alpha-Fetoproteins; C017029:asialofetuin; D004317:Doxorubicin