In vivo disposition characteristics of plasmid DNA complexed with cationic liposomes.
To control disposition and hence gene expression, we investigated the disposition characteristics of plasmid DNA complexed with the cationic liposomes Lipofectin and LipofectACE after intravenous injection in mice via the tail vein. The optimum ratios of DNA and liposome complexes were selected through in vitro cytotoxicity and transfection studies. The highest transfection was found at the DNA:liposome ratio of 1:5 w/w. Hence, this ratio was used for in vivo disposition studies, and the distribution patterns were compared with that of naked pCAT. Following intravenous injection of [32P] pCAT, radioactivity was rapidly eliminated from plasma and approximately 60% of the dose was taken up by the liver within 1.5 min. In the case of LipofectACE samples, radioactivity elimination from plasma was equally rapid, but its accumulation was observed in both the liver (35%) and the lung (45%). For Lipofectin samples, radioactivity was initially accumulated in both the liver (55%) and the lung (25%), but lung accumulation was not sustained beyond 5 min after administration. Both liposomal samples showed in vivo gene expression in the lung, heart, kidney and spleen, but not in the liver. Thus, the present study demonstrated that disposition and gene expression of pCAT can be controlled by complex formation with liposomes.
D000818:Animals; D002412:Cations; D002460:Cell Line; D002470:Cell Survival; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000493:pharmacokinetics; D004337:Drug Carriers; D004586:Electrophoresis; D015870:Gene Expression; D018014:Gene Transfer Techniques; D000882:Haplorhini; D007668:Kidney / Q000502:physiology; D008081:Liposomes; D051379:Mice; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection
D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D015500:Chloramphenicol O-Acetyltransferase