| Project/Area Number |
16590117
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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 |
Medical pharmacy
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| Research Institution | Hokkaido Pharmaceutical University |
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Principal Investigator |
MORIMOTO Kazuhiro Hokkaido Pharmaceutical University, Proffesor, 薬学部, 教授 (10113135)
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| Co-Investigator(Kenkyū-buntansha) |
CHONO Sumio Hokkaido Pharmaceutical University, Associate Reseacher, 薬学部, 助手 (90347790)
SEKI Toshinobu Hokkaido Pharmaceutical University, Associate Proffesor (60196946)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Liposome / Ciprofloxacin / Pulmonary administration / Alveolar macrophages / Respiratory infection / Drug delivery system / 呼吸器系感染症 / ドラッグデリバリーシステム |
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| Research Abstract |
In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasites infections, influence of particle size on drug delivery to alveolar macrophages (AMs) by pulmonary administration of CPFX-liposomes were investigated in rats. CPFX-liposomes were prepared with hidrogenated soybean phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In pharmacokinetic experiment, the delivery efficiency of CPFX to AMs by pulmonary administration of CPFX-liposomes to rats increased with the increase in the particle size over the range 100-1000 nm and became constant in more than 1000 nm. The concentrations of CPFX in AMs to 24 h after pulmonary administration of CPFX-liposomes (1000 nm) to rats were higher than the minimum inhibitory concentration of CPFX against various intracellular parasitism bacteria. In cytotoxic test, release of lactate dehydrogenase from lung tissues by pulmonary administration of CPFX-liposomes (1000 nm) to rats was not observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX-liposomes (1000 nm) induces an excellent antibacterial effect without cytotoxicity of lung tissues. Therefore, CPFX-liposomes may be useful in the development of drug delivery systems for treatment of respiratory infections caused by intracellular parasites such as M.tuberculosis, C.pneumoniae and L.monocytogenes.
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