Comparison between a Multifunctional Envelope-Type Nano Device and Lipoplex for Delivery to the Liver
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概要
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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.
著者
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原島 秀吉
北大院・薬学研究科
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梶本 和昭
北海道大学大学院薬学研究院
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Akita Hidetaka
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Shim Chang
Faculty Of Pharmaceutical Sciences University Of Tokyo : (present Address) College Of Pharmacy Seoul
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HARASHIMA Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Hayashi Yasuhiro
Laboratory of Innovative Nanomedicine, Graduate School of Pharmaceutical Sciences, Hokkaido Universi
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Kajimoto Kazuaki
Laboratory of Innovative Nanomedicine, Graduate School of Pharmaceutical Sciences, Hokkaido Universi
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Harashima Hideyoshi
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
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Harashima Hideyoshi
Department Of Pharmacokinetics And Pharmaceutics Graduate School Of Pharmaceutical Sciences The Univ
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Yamauchi Jun
Laboratory of Innovative Nanomedicine, Graduate School of Pharmaceutical Sciences, Hokkaido Universi
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Akita Hidetaka
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Akita Hidetaka
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Hida Yasuhiro
Department Of Surgical Oncology Hokkaido University Graduate School
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Hayashi Yasuhiro
Department Of Surgical Oncology Graduate School Of Medicine Hokkaido University
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Kajimoto Kazuaki
Department Of Epidemiology Divisions Of Preventive Medicine
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Kajimoto Kazuaki
Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Akita Hidetaka
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
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Yamauchi Jun
Laboratory of Innovative Nanomedicine, Graduate School of Pharmaceutical Sciences, Hokkaido University
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