open access

https://hdl.handle.net/2115/43076

Comparison between a Multifunctional Envelope-Type Nano Device and Lipoplex for Delivery to the Liver

英語

non-parenchymal cell

2010-05

Pharmaceutical Society of Japan

Biological & Pharmaceutical Bulletin

33(5)

926-929

The utility of using a multifunctional envelope-type nano device (MEND) for delivering a gene to the liver was examined. Lipotrust, a commercially available transfection reagent whose lipid composition is DC6-14 : DOPE : cholesterol=4 :3 :3, was used as a reference. When Lipotrust was administrated intravenously, luciferase activity of the lung was 25 times higher than that of the liver. The luciferase activity of the lung was greatly reduced when a MEND was administered, even though the lipid composition of the lipid envelope was the same in both devices. Furthermore, the luciferase activity of the liver was 5 times higher than that for lipotrust, suggesting that the encapsulation of plasmid DNA (pDNA) in liposomes is more advantageous for delivering pDNA to the liver than complex formation. The isolation of parenchymal cells (PCs) and non-parenchymal cells (NPCs) showed that the MEND system is capable of expressing the luciferase protein more preferentially in NPCs than the lipoplex system. In addition, when the surface was modified with a pH-sensitive fusogenic peptide (GALA) used as a device for endosomal escape, overall liver luciferase activity was greatly enhanced. This suggests that endosomal escape is a limiting step for the MEND system. In the case of the GALA-modified MEND, the luciferase activity of PCs and NPCs was 18 times and 11 times higher than MEND system, while the transfection efficiency of NPCs was significantly higher compared to that of PCs. Collectively, these data show that a GALA-modified MEND prepared with DC6-14 : DOPE: cholesterol represents a promising device for NPC-targeting gene delivery in vivo.

学術雑誌論文

Version of Record

0918-6158