| Project/Area Number |
15300170
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
TERADA Hiroshi Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00035544)
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO Kimiko Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40147509)
KOJIMA Shuji Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90119579)
IKEKITA Masahiko Tokyo University of Science, Faculty of Pharmaceutical Sciences, Professor, 理工学部, 教授 (70138981)
SOMA Gen-Ichiro Tokushima Bunri University, Institute for Health Science, Professor, 健康科学研究所, 教授 (00158990)
SHINOHARA Yasuo The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60226157)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | PLGA / pulmonary delivery / anti-tuberculosis agent / tuberculosis / alveolar macrophage / tuberculosis therapy / phagocytosis / DDS / 微粒子製剤 / PLGA微粒子製剤 / ファゴソーム / 薬物送達システム(DDS) / ポリ乳酸グリコール酸共重合体(PLGA) / 結核菌 / NR8383細胞株 / リファンピシン |
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| Research Abstract |
For development of the efficient therapy for overcoming tuberculosis by pulmonary delivery to alveolar macrophages of microspheres containing anti-tuberculosis agent, it is important to examine 1) characterization of microspheres necessary for efficient phagocytosis by microspheres, 2) effect of phagocytosed microspheres on the physiological conditions of macrophages, and 3) phagocytosis of microspheres delivered to alveoli and the bactericidal effect on Mycobacterium tuberculosis. Hence, the microspheres using PLGA (co-polymer consisting of lactic acid and glycolic acid) as a base, and rifampicin as an anti-tuberculosis agents were prepared by spray dry method. Then, the results shown below were obtained. 1) the 3 μm microspheres were most efficient for phagocytosis by each alveolar macrophage cell and they were well taken up by high population of macrophages in the alveoli, 2) the 3 μm microspheres did not affect the variability of macrophages and did not induce NO and TNF-a, showing that PLGA microspheres were not toxic to alveolar macrophages, and 3) PLGA microspheres were well delivered to the rat alveoli, and more than 60% of the microspheres delivered were phagocytosed by alveolar macrophages. These results showed that the pulmonary delivery of PLGA microspheres loaded with anti-tuberculosis agent will be efficient for overcoming tuberculosis.
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