In vivo disposition characteristics of plasmid DNA complexed with cationic liposomes

Ram I. Mahato, Kenji Kawabata, Yoshinobu Takakura, Mitsuru Hashida

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalJournal of Drug Targeting
Volume3
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • Cationic liposome
  • Gene therapy
  • In vivo disposition
  • Plasmid DNA
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science

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