| Project/Area Number |
23659022
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HASHIDA Yasuhiko 京都大学, 物質-細胞統合システム拠点, 特定研究員 (30512462)
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| Co-Investigator(Renkei-kenkyūsha) |
HIGUCHI Yuriko 京都大学, 大学院・薬学研究科, 助教 (40402797)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ドラッグデリバリー / ヘパリンナノ粒子 / 関節リウマチ / マクロファージ / 炎症性サイトカイン / TLR-4 |
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| Research Abstract |
This study aimed to develop a nano-sized drug carrier consisting of heparin, which has a variety of biological functions, and apply it to rheumatoid arthritis therapy. First, we conjugated native heparin or partially ring-opened heparin with sphingosine. These sphingosine-heparin conjugates form a self-assembling nanoparticle in water, which has the diameter of 120-200 nm and the ζpotential of -50 to -60 mV. Although inflammatory cytokines were produced following stimulation of mouse peritoneal macrophages with lipopolysaccharides, co-presence of the sphingosine-heparin conjugates, even without any drugs, significantly reduced the cytokine production. On the other hand, sphingosine-heparin conjugates were not effective against poly I:poly C-induced TNF-α production, suggesting that the conjugates act selectively on the TLR4/NF-κB pathway. In the mouse model of type II collagen-induced arthritis, the sphingosine-heparin conjugates, especially that derived from partially ring-opened heparin, showed remarkable anti-inflammatory effects.
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