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The purpose of this study was to examine the effect of the size of galactosylated cationic liposome (Gal-liposome)/plasmid DNA complex (Gal-lipoplex) on hepatocyte-selective gene transfection after intraportal administration. pCMV-Luc was selected as a model plasmid DNA. After intraportal administration of Gal-lipoplex to mice, the hepatic and intrahepatic gene expression was evaluated. To evaluate the effect of size, three different sizes of Gal-liposome were prepared. The mean particle sizes of Gal-lipoplex were about 141, 179, and 235 nm, respectively. The hepatic transfection efficacy was significantly enhanced by increasing the size of Gal-lipoplex. However, the gene expression in liver parenchymal cells (PC) of Gal-lipoplex of about 141 nm in size was significantly higher than that in liver non-parenchymal cells (NPC). In contrast, gene expression in PC of Gal-lipoplex of about 235 nm in size was significantly lower than that in NPC. These results highlight the importance of the Gal-lipoplex size for hepatocyte-selective gene transfer in vivo. The information in this study will be valuable for the future use, design, and development of Gal-lipoplex for in vivo applications.

Effect of the Particle Size of Galactosylated Lipoplex on Hepatocyte-Selective Gene Transfection after Intraportal Administration