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タイトル: Bone-Targeting of Quinolones Conjugated with an Acidic Oligopeptide
著者: Takahashi, Tatsuo
Yokogawa, Koichi
Sakura, Naoki
Nomura, Masaaki
Kobayashi, Shinjiro
Miyamoto, Kenichi
宮本, 謙一
発行日: 2008年12月12日
出版社(者): Springer Verlag (Germany)
雑誌名: Pharmaceutical Research
ISSN: 0724-8741
巻: 25
号: 12
開始ページ: 2881
終了ページ: 2888
キーワード: acidic oligopeptide
drug delivery system
levofloxacin
norfloxacin
osteomyelitis
抄録: Purpose: Osteomyelitis is a progressive infectious process resulting in inflammatory destruction and necrosis of bone. The long-term administration of high-dosage antibiotics is required to treat osteomyelitis, owing to the limited distribution of antibiotics within bone. Therefore, targeted delivery of antibiotics to bone promises to improve therapeutic effectiveness. Methods: We synthesized quinolones such as levofloxacin and norfloxacin conjugated to an acidic oligopeptide, which works as a bone-targeting carrier after systemic administration. The therapeutic effectiveness of the conjugated quinolones in osteomyelitis was evaluated using a mouse model of osteomyelitis, created by inoculating Staphylococcus aureus into the tibia of mice. Results: With intravenous injection, the conjugated quinolones selectively distributed to bone, reaching concentrations up to 100-fold those of non-conjugated quinolones. Single intravenous injection of levofloxacin as well as conjugated levofloxacin exhibited antibiotic effects in the osteomyelitis mouse model; conversely, neither conjugated nor non-conjugated norfloxacin was effective. The antibiotic effect of conjugated levofloxacin persisted to at least 6 days after injection, whereas the effect of non-conjugated levofloxacin was temporary. Conclusion: The selective bone delivery of quinolones conjugated with an acidic oligopeptide may be effective in treating osteomyelitis, although the resulting concentration of antibiotic may be insufficient to completely kill S. aureus. © 2008 Springer Science+Business Media, LLC.
DOI: 10.1007/s11095-008-9605-4
URI: http://hdl.handle.net/2297/11777
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文

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