文章基本信息

标题：Comparison between a Multifunctional Envelope-Type Nano Device and Lipoplex for Delivery to the Liver
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作者：Jun Yamauchi ; Yasuhiro Hayashi ; Kazuaki Kajimoto 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：5
页码：926-929
DOI：10.1248/bpb.33.926
出版社：The Pharmaceutical Society of Japan
摘要：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 NPCtargeting gene delivery in vivo .
关键词：multifunctional envelope-type nano device;lipoplex;liver gene delivery;pH-sensitive fusogenic peptide;nonparenchymal cell