title: Targeting of stabilized plasmid lipid particles to hepatocytes in vivo by means of coupled lactoferrin.
abstract: For non-viral gene delivery we prepared stabilized plasmid lipid particles (SPLPs), to which lactoferrin (LF) was coupled as a hepatocyte specific targeting ligand. LF-SPLPs and untargeted SPLPs labeled with [3H]cholesteryloleyl-ether were injected into rats. About 87% of the LF-SPLPs were eliminated from the blood within 5 min, while 80% of untargeted SPLPs were still circulating after 2 h. Fifty-two percent of the LF-SPLPs were taken up by hepatocytes, while non-parenchymal liver cells accounted for 16% of the uptake. Despite the efficient targeting of LF-SPLPs to hepatocytes and their capacity to transfect HepG2 and COS-7 cells in vitro, expression of a reporter gene was not detected in vivo. Overall, covalent coupling of LF to SPLPs leads to massive delivery in hepatocytes after systemic administration. However, these LF-SPLPs are not able to transfect these cells in vivo.
authors.affiliation: Medical Biology Section, Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. a.h.weeke-klimp@med.umcg.nl
authors.forename: Alida H
authors.initials: AH
authors.lastname: Weeke-Klimp
authors.forename: Martin
authors.initials: M
authors.lastname: Bartsch
authors.forename: Henriëtte W M
authors.initials: HW
authors.lastname: Morselt
authors.forename: Ingrid
authors.initials: I
authors.lastname: Van Veen-Hof
authors.forename: Dirk K F
authors.initials: DK
authors.lastname: Meijer
authors.forename: Gerrit L
authors.initials: GL
authors.lastname: Scherphof
authors.forename: Jan A A M
authors.initials: JA
authors.lastname: Kamps
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D010957:Plasmids; D051381:Rats; D014162:Transfection
chemical_list: D008055:Lipids; D007781:Lactoferrin