Development of Medically ApplicableLiposomes as Enzyme or Drug Carriers
| Project/Area Number |
58870126
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
医学一般(含病院管理学・看護学・人類遺伝学・病態検査学・実験動物)
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
1983 – 1985
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| Project Status |
Completed (Fiscal Year 1985)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1985: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1984: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1983: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Liposomes / entrapment / glycolipids / targeting / enzyme deficiency / 酵素欠損症 |
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| Research Abstract |
The incorporation into liver of the negative unilameller liposomes (PC/Chol/DCP, molar ratio 4:5:1) containing invertase in the aqueous compartment and ( <^(14)C> )tripalmitin in the lipid bilayer as marker was examined after intravenous injection into mouse. The rate of uptake by the liver of the liposomes reached a maximum liver 1 hr after injection and then gradually declined as examined by radioactivity of ( <^(14)C> )tripalmitin. On the other hand, the invertase activity in the liver was gradually increased up to 2 hr and remained fairly constant during 15 hr thereafter. Subcellular fractionation of the mouse liver loaded with the liposomes showed a predominant localization of liposomal lipid radioactivity and invertase activity in the lysosome-rich fraction. Liposomes with radioactive tripalmitins are considered to be taken up by liver via endocytosis and subsequently delivered into lysosomes. The intrahepatic fate of the radioactive tripalmitin in liposomes indicated that they were rapidly degraded by lysosomal lipase to free fatty acids, which were reutilized for synthesis of phospholipids in endoplasmic reticulum. The administration of the liposomes containing E-64, a potent lysosomal protease inhibitor, was able to protect the intralysosomal degradation of the injected enzymes via liposomes.
Lactosylceramide (LacCer) or asialofetuin sugar chain (AFSC) induced an increment of the liposomal uptake into the liver when these markers were incorporated in DMPC or DPPC-based but not in eggPC liposomes. This suggested an involvement of liposomal membrane fluidity in the liver uptake. LacCer or AFSC increased liposomal uptake in the isolated parenchymal cells, although they were ineffective for isolated Kupffer cells. Such enhancing effect of LacCer was abolished by the addition of AF, suggesting evidence for a galactose-specific receptormedicated endocytosis.
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Report
(1 results)
Research Products
(10 results)
