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Pharmazie. 2004 May;59(5):405-8.

Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice.

Author information

1
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.

Abstract

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.

PMID:
15212310
[Indexed for MEDLINE]

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