Utility of the three-dimensional cultured human skin model as a tool to evaluate rapid determination of skin permeation of drag and skin irritation.
| Project/Area Number |
12672157
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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 |
医薬分子機能学
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| Research Institution | Josai University |
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Principal Investigator |
SUGIBAYASHI Kenji Faculty of Pharmaceutical Sciences, Josai University, Professor, 薬学部, 教授 (00105834)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIBASHI Takuya Tsuruga Institute of Biotechnology, TOYOBO Co. Ltd., Chief Researcher, 敦賀バイオ研, 主席部員
TAKAYAMA Kozo Department of Pharmaceutics, Hoshi University, Professor, 薬学部, 教授 (00130758)
HASEGAWA Tetsuya Faculty of Pharmaceutical Sciences, Josai University, Assistant, 薬学部, 助手 (50245148)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | three-dimensional cultured human skin model / Skin permeation / high throughput screening / alternative skin / penetration enhancement / quartz crystal microbalance / skin irritation / MTT assay / 三次元培養ヒト皮膚モデル / High Throughput Screening / skin permeation / high throughput screening / 経皮吸収促進剤 / skin metabolism |
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| Research Abstract |
Three-dimensional cultured human skin model (LSE-high) was evaluated for prediction of skin permeation of drugs. Although the cumulative amount of drags that permeated through LSH-high was about 10-fold higher than those through the excised human and hairless rat skin, a good correlation was found the LSE-high and excised skin permeabilities. Effect of penetration enhancers on the permeation of drugs across LSE-high was also evaluated. Every enhancer showed a penetration-enhancing effect on the drug permeation through LSE-high as it did through the hairless rat skin. These findings suggest that LSE-high may be utilized as an alternative membrane when testing the promoting effect of penetration enhancers on the skin permeation of drugs. Additionally, a quartz crystal microbalance was tested for a rapid measuring method of permeation of drug through a living dermal model. The obtained values corrected by decomvolution were very closed to that by HPLC.
A cytotoxicity assay using a LSE-high was evaluated. When the irritants were applied on the LSE-high, two first ordered decreasing phases, initial slow land following rapid phases, were found in the viability of LSE. The inflection time point from the slow to rapid rate was dependent on the kind and concentration of irritants applied, suggesting that the skin irritation rate is closely related by the barrier function of skin. LSE-high was also evaluated as an alternative to the Draize skin irritation using animals. Irritant concentration showing IC50 was similar for the MTT assay and Draize test. In contrast, IC50 for MTT assay in LSE was much lower than that using guinea pig skin. We than corrected the results for the MTT assay using a ratio of IC50 in gunea pig skin against LSE, resulting in a good relation between both MTT results in guinea pig skin and LSE-high.
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Report
(3 results)
Research Products
(11 results)
