| Project/Area Number |
20550027
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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 |
Physical chemistry
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| Research Institution | Himeji Dokkyo University |
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Principal Investigator |
OKAMURA Emiko 姫路獨協大学, 薬学部, 教授 (00160705)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHII Noriyuki 姫路獨協大学, 薬学部, 准教授 (70371599)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 生物物理化学 / 熱揺らぎ / ドラッグデリバリー / 脂質二分子膜 / パルス磁場勾配NMR / 拡散 / 生物物理 / 表面・界面物性 / 動態 / パルス磁場勾配 NMR |
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| Research Abstract |
Drug delivery to biomembranes is crucial as a primary stage of the bioactivity in the cell. Lipid bilayer membrane is a dynamic structure where molecules are always fluctuating under physiological conditions. The mechanism of drug delivery is related to the molecular dynamics in such soft, fluid membrane interface. To gain insight into molecular movements in membranes, we develop a noninvasive method to monitor dynamic properties of drugs and lipid components in membranes by applying multinuclear high-resolution solution NMR in combination with the pulsed-field-gradient(PFG) technique. We have quantified the diffusivity, the kinetics of membrane binding, and the bound fraction of the drug in situ by using large unilamellar vesicles of egg phosphatidylcholine as model cell membranes. The combination of one-dimensional and PFG NMR serves to quantify the kinetics of membrane binding where the bound and the free components are unable to distinguish because of the rapid exchange on the NMR time scale. A small-sized 5-fluorouracil and fluorinated bisphenol A, and a pentapeptide enkephalin are used as a model drug.
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