title: Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells.
abstract: Human serum albumin (HSA) derivatized with cis-aconitic anhydride was covalently coupled to liposomes with a size of approximately 100 nm [polyaconitylated HSA (Aco-HSA) liposomes]. Within 30 min after injection into a rat, Aco-HSA liposomes were completely cleared from the blood and almost exclusively taken up by the liver, whereas in control liposomes 80% was still present in the blood at that time. Endothelial cells were shown to account for almost two-thirds of the hepatic uptake of the Aco-HSA liposomes, the remainder being recovered mainly in the liver macrophages (Kupffer cells). With fluorescently labeled liposomes it was shown that the Aco-HSA liposomes target a vast majority (>85%) of the cells in the endothelial cell population. Control liposomes were not taken up to a significant extent by the endothelial cells. Uptake of Aco-HSA liposomes by both endothelial and Kupffer cells was inhibited by preinjection with polyinosinic acid, indicating the involvement of scavenger receptors in the uptake process. The uptake of Aco-HSA liposomes by liver endothelial cells was dependent on liposome size; with increasing liposome diameter endothelial cell uptake decreased in favor of Kupffer cell uptake. We have demonstrated that massive in vivo targeting of liposomes to a defined cell population other than macrophages is possible. Aco-HSA liposomes thus may represent an attractive drug carrier system for treatment of various liver or liver endothelium-associated disorders.
authors.affiliation: Department of Physiological Chemistry, Groningen Utrecht Institute for Drug Exploration (GUIDE), Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands. j.a.a.m.kamps@med.rug.nl
authors.forename: J A
authors.initials: JA
authors.lastname: Kamps
authors.forename: H W
authors.initials: HW
authors.lastname: Morselt
authors.forename: P J
authors.initials: PJ
authors.lastname: Swart
authors.forename: D K
authors.initials: DK
authors.lastname: Meijer
authors.forename: G L
authors.initials: GL
authors.lastname: Scherphof
mesh_terms: D000156:Aconitic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines; D011069:Poly I / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D000075462:Serum Albumin, Human; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D012709:Serum Albumin; C108785:polyaconitylated human serum albumin; D014316:Tritium; D011069:Poly I; C023511:cholesteryl oleyl ether; D000156:Aconitic Acid; D002784:Cholesterol; D000075462:Serum Albumin, Human