Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice.
The purpose of this study was to evaluate the effect of cationic charge of complexes after intravenous administration of cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiomannosyl-ethyl)amino]butyl]formamide (Man-C4-Chol) containing cationic liposomes/pDNA complexes in mice. Transfection efficiency after intravenous administration of complex at a charge ratio (- : +) of 1.0:2.3 and/or 1.0:3.1 in liver and spleen expressing a mannose receptor on the cell surface were higher than those in lung. When complexes were formed at a charge ratio (- : +) of 1.0:4.7, on the other hand, transfection efficiency in the lung was highest, suggesting a non-specific interaction. Although asialoglycoprotein receptors are expressed on hepatocytes, a liver-selective gene transfection was not achieved by the intravenous administration of pDNA complexed with cholesten-5-yloxy-N-[4-[(1-imino-2-D-thiogalactosyl-ethyl)-amino]butyl]formamide (Gal-C4-Chol)/DOPE liposomes at a charge ratio (- : +) of 1.0 : 2.3. This information supports the design of pDNA/ligands-grafted cationic liposome complexes for cell-specific gene delivery after intravenous administration.
Kawakami
S
S
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Hattori
Y
Y
Lu
Y
Y
Higuchi
Y
Y
Yamashita
F
F
Hashida
M
M
D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers; D015870:Gene Expression; D007275:Injections, Intravenous; D037181:Lectins, C-Type / Q000187:drug effects; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects*; D014162:Transfection
D002412:Cations; D004337:Drug Carriers; D037181:Lectins, C-Type; D008081:Liposomes; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D004247:DNA; D008156:Luciferases