Strategic approach based on molecular mechanism for modulation of barrier function of tight junction to enhance delivery of new biopharmaceuticals
| Project/Area Number |
25460222
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Makiko 日本大学, 薬学部, 教授 (50199296)
KOIZUMI Naoya 昭和薬科大学, 薬学部, 講師 (80433845)
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| Co-Investigator(Renkei-kenkyūsha) |
KONDOH Masuo 大阪大学, 大学院薬学研究科, 准教授 (50309697)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 生体膜透過制御機構 / 生体膜透過バリアー機能 / 高分子薬物透過促進 / タイトジャンクション / バイオ医薬品DDSの基礎研究 / 吸収促進法 / 生体膜透過制御 |
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| Outline of Final Research Achievements |
Aim of the present study was to investigate the method for modulation of barrier function of tight junction (TJ) in epithelial cells to enhance delivery ofnew biopharmaceuticals. We studied the time course of electrical conductivity (Σ) in MDCK and Caco-2 cells upon treatment with modulators, the C-terminus fragments of clostridium perfringens enterotoxin and sodium caprate (C10). Percolation is the operative mechanism for increase in Σ through TJ modulation. Sec61β overexpression increased TJ modulation rates, in conjunction with enhanced delivery of claudin-4 from and to plasma membranes. Sec61β may be a novel TJ modulation target, including modulation rates for drug delivery system. For gene transfer into cells, the binding ability of adenovirus (Ad) vectors with the receptor (CAR) was found to be important. A novel gene transfer method using transduction with Ad vectors in the presence of C10 led more efficiently to gene expression in Caco-2 cells than Ad vector alone.
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Report
(4 results)
Research Products
(14 results)
