| Project/Area Number |
14580836
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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 |
Biomedical engineering/Biological material science
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
MAKINO Kimiko Faculty of Pharmaceutical Sciences, Tokyo University of Science, Full Professor, 薬学部・製薬学科, 教授 (40147509)
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| Co-Investigator(Kenkyū-buntansha) |
SOMA Gen-ichiro Institute for Health Sciences, Tokushima Bunri University, Full Professor, 健康科学研究所, 教授 (00158990)
TERADA Hiroshi Faculty of Pharmaceutical Sciences, Tokyo University of Science, Full Professor, 薬学部・製薬学科, 教授 (00035544)
OHSHIMA Hiroyuki Faculty of Pharmaceutical Sciences, Tokyo University of Science, Full Professor, 薬学部・製薬学科, 教授 (60176873)
KOJIMA Shuji Faculty of Pharmaceutical Sciences, Tokyo University of Science, Full Professor, 薬学部・製薬学科, 教授 (90119579)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | alveolar macrophages / PLGA / microsphere / phagocytosis / tuberculosis / 肺結核 / 貧食 |
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| Research Abstract |
Purpose : Tuberculosis is recognized as a global republic health emergency by the declare of World Health Organaization on 23 April 1993. Microsphere technology has been used to treat initial infection with M tuberculosis so that multiple-drug-resistant strains do not develop. Slow release of rifampicin from microspheres localized in alveolar macrophages is ideal to treat the disease, since tubercle bacillus is a facultative intracellular parasite and microspheres can penetrate into the macrophages by phagocytosis. Methods : NR8383 cell lines either infected or uninfected by BCG were used.
Poly(lactide/glycolide) (PLGA) with the molecular weights of 5000, 10000, and 20000 were used to prepare microspheres.Monodis perse rifainpicin(RFP)-loaded PLGA microspheres were prepared by solvent evaporation method with Shirasu porous glass membranes.Results : RFP-loaded PLGA microspheres with the diameters in the range of 1~10 micrometers were prepared. Microspheres with the diameter of 3 micrometers were most effectively phagocytosed by NR8383 cells.The molecular weights of PLGA did not affect the ratio of phagocytic uptake.The intracellular concentration of RFP when RFP-loaded PLGA microspheres were added to the cells was observed to be 20 times higher than that when the same amount of RFP was added as a solution.RFP was released from PLGA microspheres with the molecular weight of 5000 or 10000 within 1 week. Conclusions : We have found that PLGA microspheres stimulate the M tuberculosis-infected alveolar macrophages and then RFP-loaded PLGA microspheres with the average diameters of 3 micrometers effectively decrease the survival rates of M tuberculosis in the macrophages.
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