2019 Fiscal Year Final Research Report
Development of safety evaluation system for DDS carrier based on network toxicology
| Project/Area Number |
16H01861
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical engineering assessment
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山下 富義 京都大学, 薬学研究科, 教授 (30243041)
樋口 ゆり子 京都大学, 薬学研究科, 准教授 (40402797)
杉山 直幸 京都大学, 薬学研究科, 准教授 (50545704)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 安全性評価 / DDS / 薬物動態学 |
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| Outline of Final Research Achievements |
In the development of DDS, the molecular mechanism of off-target effects has not been discussed enough. This project aims to establish an evaluation system for DDS based on analytical science, informatics, and genomics/proteomics analysis. Transcriptional factors were selected by analyzing databases of drug-induced liver injury and transcriptional factor binding sites. In addition, three proteins with a significant variation in phosphorylation in the liver after administration of DDS formulation were identified by LC/MS/MS. Based on the combinatory analysis of these data, we established CREB reporter assay system and evaluated DDS formulation by the system.
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| Free Research Field |
人間医工学、医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
DDS開発において、体内動態制御と薬効エンドポイントのみがに注目したされて治療効果製剤機能の有効性の評価が優先がなされてきた。本研究の成果により、高感度・網羅的分析とシミュレーションを活用したによる治療システムの安全性評価に関する研究が進むことにが進展期待できする。また、がんや希少疾患など難治性疾患に対する治療戦略において、患者QOL・安心を考えた安全性保証と標的指向性を兼ね備えたDDS製剤の開発に貢献するものと期待される。
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