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

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

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.

MeSH terms

  • Animals
  • Cations
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry, Physical
  • DNA / administration & dosage
  • DNA / genetics
  • Drug Carriers
  • Gene Expression
  • Injections, Intravenous
  • Lectins, C-Type / drug effects
  • Liposomes
  • Luciferases / genetics
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mannose-Binding Lectins / drug effects
  • Mice
  • Mice, Inbred ICR
  • Particle Size
  • Plasmids / chemistry
  • Plasmids / genetics*
  • Receptors, Cell Surface / drug effects
  • Receptors, Drug / drug effects*
  • Transfection

Substances

  • Cations
  • Drug Carriers
  • Lectins, C-Type
  • Liposomes
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, Drug
  • mannose receptor
  • DNA
  • Luciferases