2011 Fiscal Year Final Research Report
Studies of barrier function of tight junction in epithelial celllayers and strategic development of novel methods for drug permeation enhancement in cells
| Project/Area Number |
21590178
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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 |
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 昭和薬科大学, 薬学部, 准教授 (50199296)
KOIZUMI Naoya 昭和薬科大学, 薬学部, 助教 (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) |
2009 – 2011
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| Keywords | 生体膜透過バリアー機能 / 薬物透過制御法 / 生体機能利用 |
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| Research Abstract |
The aim of this study was to evaluate the barrier function of tight junction(TJ) in epithelial cell layers and to develop novel methods for drug permeation enhancement in cells.
We investigated the expression profiles of gene and the changes in gene expression in Caco-2 cells, when the C-terminal fragment of Clostridium perfringens enterotoxin(C-CPE), a permeation enhancement modulator targeted to claudins playing a pivotal role in the barrier function of TJ, was applied in cell monolayers. The formation of TJ barriers in Caco-2 monolayers was monitored by the transepithelial resistance(TER) assay. We investigated approximately 45, 000 genes. The expression of 106 genes was increased in 4 times, whereas the expression of 182 genes was decreased in 1/4, when TJ barrier function was decreased by the treatment of C-CPE.
We focused the macropinocytosis induced by adenovirus(Ad) vector for drug delivery, because macropinocytosis can be used delivery of macromolecules, nanoparticles, and so on. It was found that macropinocytosis induced by the fiber shaft protein of Ad type 35(Ad35 Shaft) can be delivered a model of macromolecular drug, FITC-dextran(M. W. 40, 000) in HepG2 cells. Also, we observed the Ad35 Shaft-mediated gene expression of plasmid transduction into HepG2 cells. These results suggested that the fiber shaft protein, especially Ad35 Shaft, is a useful tool for the systems of macromolecular drug therapy and gene delivery into cells.
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