title: Selective uptake of liposomes containing lactose mono-fatty acid derivatives by hepatic parenchymal cells.
abstract: In this study we investigated the hepatic uptake of liposomes containing a novel synthetic glycolipid, lactose mono-arachidic acid amide (LAA). Liposomes containing LAA were aggregated by Ricinus communis agglutinin from caster bean, while the control liposomes were not, and the results suggested that the galactose residues of LAA were exposed to the outer surface of the liposomes. Next, the blood clearance and hepatic uptake of liposomes containing LAA after intravenous administration were compared with those of the control liposomes in rat. Hepatic uptake of liposomes containing LAA was greater than that of the control liposomes, rising significantly with dose. As a result of separation of the parenchymal and non-parenchymal cells, it was shown that the increase in hepatic uptake was mostly accounted for by a greater uptake by parenchymal cells. The inhibitory activity of asialofetuin on the hepatic uptake of liposomes containing LAA suggested that a galactose-specific recognition is involved in this uptake. These results demonstrate that the lactose mono-fatty acid amides (LFAs) are promising novel compounds for the introduction of carbohydrate residues onto the liposomal surface and that liposomes containing LFAs are potential carriers for the selective delivery of drugs to specific cells.
authors.affiliation: Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamauchi
authors.forename: H
authors.initials: H
authors.lastname: Kikuchi
authors.forename: M
authors.initials: M
authors.lastname: Sawada
authors.forename: M
authors.initials: M
authors.lastname: Tomikawa
authors.forename: S
authors.initials: S
authors.lastname: Hirota
mesh_terms: D000577:Amides / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004537:Eicosanoic Acids / Q000097:blood / Q000493:pharmacokinetics; D005227:Fatty Acids / Q000097:blood / Q000493:pharmacokinetics*; D060748:Fetuins; D006017:Glycolipids / Q000097:blood / Q000493:pharmacokinetics*; D008081:Liposomes / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000494:pharmacology
chemical_list: D000577:Amides; D001212:Asialoglycoproteins; D004537:Eicosanoic Acids; D005227:Fatty Acids; D060748:Fetuins; D006017:Glycolipids; D008081:Liposomes; D000509:alpha-Fetoproteins; C017029:asialofetuin