| Project/Area Number |
12470488
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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 |
HANDA Tetsurou HANDA,Tetsurou, 薬学研究科, 教授 (00025719)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Minoru KYOTO UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, INSTRUCTOR, 薬学研究科, 助手 (70314226)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | lipid nanoparticle / cubosomes / hexosomes / emulsions / plasma protein / monoolein / phosphatidylcholine / cell association / 膜脂質ナノ粒子 / 血漿タンパク質 / 曲げのストレス / アポリポタンパク質 / リポタンパク質リパーゼ / 血漿蛋白質 / アルブミン / リパーゼ / 体内挙動 / プラズマ蛋白質 / アポリポ蛋白質 / リポ蛋白質リパーゼ / 非2分子膜 / 自発的曲率 / 両親媒性構造 |
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| Research Abstract |
Novel aqueous dispersions of lipid nanoparticles with bicontinuous cubic (cubosomes) or hexagonal (hexosomes) liquid crystals in their interior were prepared by a high pressure emulsification. Small-angle X-ray scattering experiments confirmed the presence of cubic or hexagonal structures inside depend upon the monoolein/oleic acid-composition. ^13C NMR experiments with paramagnetic shift reagent showed that the signal of carbonyl carbon of oleic-1-^13C acid in the particles readily shifted to a lower magnetic field by addition of Eu^<3+>, indicating high accessibility of the ion into the water channel inside the particles. To understand behaviors in plasma of lipid nanoparticles; cubosomes, hexosomes, emulsions and vesicles, the effects of lipid composition and surface structure on the protein interaction were evaluated. Monoolein in cubosomes and hexosomes was extracted by plasma proteins and particles rapidly changed into sm emnants. Core lipids in emulsions played roles in determining the binding behavior of apolipoproteins A-1 and E at the particle surface: ^13C NMR and fluorescence measurements showed that the acyl chain region of phosphatidylcholine (PC) at emulsion surface monolayers is more restricted than those of vesicle PC bilayers, whereas the PC head group region of emulsions is more hydrated. Accordingly, interpenetration of core lipids into surface PC monolayers was presumed to occur in lipid emulsions. The interpenetration causes the separation of PC head groups and leads to enhanced apoA-1 or E binding at emulsion surface. Lipid risk factors, cholesterol, its ester, sphingomyelin and ceramide. modified the structure of surface monolayers, leading to the different protein binding and cell association.
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