| Project/Area Number |
13470477
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HASHIDA Mitsuru Kyoto University, Graduate Sch. Pharm. Sci., Professor, 薬学研究科, 教授 (20135594)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Makiya Kyoto University, Graduate Sch. Pharm. Sci., Associate Professor, 薬学研究科, 助教授 (40273437)
YAMASHITA Fumiyoshi Kyoto University, Graduate Sch. Pharm. Sci., Associate Professor, 薬学研究科, 助教授 (30243041)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥11,700,000 (Direct Cost: ¥11,700,000)
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| Keywords | Drug delivery / Targeting / DDS / Liposome / Sugar modification / Endocytosis / Receptor-mediated / Biodistribution |
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| Research Abstract |
Although liposomes are focused on the drug and gene carriers, it is essential to develop the novel effective and cell-selective carrier systems for the clinical application of the various types of drugs. In the present study, we evaluated the novel surface modified liposomes for the purpose of development the advanced liposomes, which possessed the cell-selective properties or controlled interaction with endogenous component. In the present study, we synthesized novel galactosylated and mannosylated cholesterol derivatives for drug and gene delivery to liver parenchymal cell and non-parenchymal cell, respectively. These derivatives possess bi-functional properties i.e. cholesterol for the fix the sugar moiety on liposomal surface and a sugar residue for the cell surface receptors. In vitro study demonstrated that the glycosylated liposomes were efficiently taken up the receptor-mediated endocytosis. After intravenous administration, glycosylated liposomes were effectively taken up by the cells, which expressed the receptor. We also prepared the glycosylated cationic liposomes/plasmid DNA complexes for the liver cell-selective gene delivery. Receptor-mediated gene delivery systems are able to introduce foreign DNA into specific cell types in vivo. However, we have confirmed that not only the nature of the ligands grafted to carriers but also the lipid composition and physicochemical properties of the complexes need to be optimized for effective cell-selective targeting of plasmid DNA. In conclusion, we developed the novel cell-selective drug and gene carriers, which can be controlled the biodistribution of drug and gene.
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