Tissue and intrahepatic distribution and subcellular localization of a mannosylated lipoplex after intravenous administration in mice.
We have previously reported that, unlike a lipoplex and mannosylated (Man) lipoplex underwent gene transfer to liver nonparenchymal cells (NPC) that possess mannose receptors after intravenous administration in mice. In this study, the tissue, intrahepatic distribution, and subcellular localization of the lipoplex after intravenous administration were investigated. DC-Chol liposome was selected as a cationic liposomes. After administration of lipoplex and Man lipoplex, the high gene expression was observed in the lung and liver, respectively. After administration of [32P]Man lipoplex, about 80% of [32P]plasmid DNA (pDNA) was accumulated in the liver. As for the intrahepatic distribution, the NPC/parenchymal cells (PC) ratio of [32P]Man lipoplex was 9.64, whereas the NPC/PC ratio of [32P]lipoplex was 1.93. The radioactivity in the cytosolic fraction of liver homogenate of [111In]Man lipoplex was two-fold higher than that of [111In]lipoplex, indicating that Man liposomes facilitate the release of pDNA into the cytosolic space. However, a rapid sorting of the radioactivity from endosomes to lysosomes was observed with the [111In]Man lipoplex. Also, amplification of pDNA by PCR suggested that the Man lipoplex is more rapidly degraded within the intracellular vesicles than the lipoplex. These results suggested that modulation of its intracellular sorting could improve the transfection efficiency of Man lipoplex.
Yamada
Makiko
M
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, 606-8501, Japan.
Nishikawa
Makiya
M
Kawakami
Shigeru
S
Hattori
Yoshiyuki
Y
Nakano
Takayuki
T
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008358:Mannose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008813:Mice, Inbred ICR; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D008081:Liposomes; D008358:Mannose