Effect of the particle size of galactosylated lipoplex on hepatocyte-selective gene transfection after intraportal administration.
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.
Higuchi
Yuriko
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Kawakami
Shigeru
S
Fumoto
Shintaro
S
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D005260:Female; D005697:Galactosides / Q000493:pharmacokinetics*; D015870:Gene Expression; D022781:Hepatocytes / Q000502:physiology*; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D011168:Portal System / Q000502:physiology*; D014162:Transfection / Q000379:methods*
D005697:Galactosides; D008081:Liposomes