| Project/Area Number |
10672100
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Mukogawa Women's University |
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Principal Investigator |
TAKAHASHI Koichi Mukogawa Women's University, School of Pharmacy, Professor, 薬学部, 教授 (00179483)
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| Co-Investigator(Kenkyū-buntansha) |
MAYUMI Tadanori Osaka University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00098485)
NUMATA Nanako Mukogawa Women's University, School of Pharmacy, Technician, 薬学部, 助手 (60291811)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | fusogenic liposomes / nasal mucosa / tracheal mucosa / sialidase / trypsin-type endoprotease / リポソーム / センダイウイルス |
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| Research Abstract |
The objective of the present investigation was to evaluate the usefulness and characterization of fusogenic liposomes (FLs), which have envelope glycoproteins of the Sendai virus on their surface, on a delivery of macromolecules to respiratory mucosa.
After nasal administration of FLs and unilaminar liposomes (Lips) containing FITC-dextran (FD) as a model macromolecular compound, FD was not detected in plasma at any times. The recovery of FD after administration of Fls to nose and trachea was significantly lower than that of FD solution or Lips. Time course analysis showed that the rapid fusion to the mucosa in FLs was detectable within 15 min in nose and 30 min in trachea, and reached a maximum value at 30 min in nose and 60 min in trachea. The molecular weights of FD did not affect the binding and fusion of FLs to the mucosa. As evaluated by confocal laser scanning fluorescence microscopy, uptake studies revealed intracellular fluorescence in the epithelial cells. The binding and fusion of FLs to the mucosa were decreased with the coadministration of DTT and pretreatment of sialidase. These results suggested that FLs may recognize sialic acid in the process of the binding and fusion. The binding amount of cationic FLs to nasal mucosa was larger than of anionic FLs, but the fusion amount was almost same between cationic and anionic FLs. Protease inhibitors, such as sialidase inhibitor, typsin inhibitor and chamostat, increased the binding and fusion amount of FLs to the mucosa, but bacitracin did not. From these results, FLs may be useful in localizing macromolecules to nasal mucosa.
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