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 the disposition and gene expression of pCAT can be controlled by complex formation with liposomes.