Bone-targeting of quinolones conjugated with an acidic oligopeptide
Abstract
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…
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