| Project/Area Number |
21790051
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Mukogawa Women's University |
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Principal Investigator |
KURODA Yukihiro Mukogawa Women's University, 薬学部, 准教授 (60314225)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | ホスホリピドーシス / マクロファージ / リポソーム / 塩基性薬物 / 両親媒性薬物 / カチオン性両親媒性薬 / リン脂質の取り込み / RAW264 / スカベンジャー受容体 / 酸性ベクシル / カチオン性両親媒性薬物 / 酸性ベシクル / リモートローディング / 弱塩基 |
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| Research Abstract |
The mechanism of drug-induced phospholipidosis is unclear. Among hypotheses proposed, two were examined in the present study: i) excessive cellular uptake of phospholipids and ii) neutralization of acidic vesicles by drug accumulation. Phospholipid content in the cells increased by treatment of phospholipidosis-inducing drugs as measured by DiI phospholipid probe. Increased cellular phospholipid accumulation did not decrease following treatment with inhibitors of taking-up pathways. Regardless of their phospholipidosis-inducing potential, drugs characterized by a high pKa value effectively accumulated in liposomes. This accumulation caused an upward shift of the interior pH of liposomes, which was independent of phospholipidosis-inducing potential of drugs.
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