Targeting of stabilized plasmid lipid particles to hepatocytes in vivo by means of coupled lactoferrin.
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.
Weeke-Klimp
Alida H
AH
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
Bartsch
Martin
M
Morselt
Henriëtte W M
HW
Van Veen-Hof
Ingrid
I
Meijer
Dirk K F
DK
Scherphof
Gerrit L
GL
Kamps
Jan A A M
JA
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
D008055:Lipids; D007781:Lactoferrin