Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax


Autoři: Chad W. Stratilo aff001;  Scott Jager aff001;  Melissa Crichton aff001;  James D. Blanchard aff002
Působiště autorů: Bio Threat Defence Section, Suffield Research Centre, Defence Research and Development Canada, Ralston, Alberta, Canada aff001;  Aradigm Corporation, Hayward, California, United States of America aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0228162

Souhrn

The in vivo efficacy of liposomal encapsulated ciprofloxacin in two formulations, lipoquin and apulmiq, were evaluated against the causative agent of anthrax, Bacillus anthracis. Liposomal encapsulated ciprofloxacin is attractive as a therapy since it allows for once daily dosing and achieves higher concentrations of the antibiotic at the site of initial mucosal entry but lower systemic drug concentrations. The in vivo efficacy of lipoquin and apulmiq delivered by intranasal instillation was studied at different doses and schedules in both a post exposure prophylaxis (PEP) therapy model and in a delayed treatment model of murine inhalational anthrax. In the mouse model of infection, the survival curves for all treatment cohorts differed significantly from the vehicle control. Ciprofloxacin, lipoquin and apulmiq provided a high level of protection (87–90%) after 7 days of therapy when administered within 24 hours of exposure. Reducing therapy to only three days still provided protection of 60–87%, if therapy was provided within 24 hours of exposure. If treatment was initiated 48 hours after exposure the survival rate was reduced to 46–65%. These studies suggest that lipoquin and apulmiq may be attractive therapies as PEP and as part of a treatment cocktail for B. anthracis.

Klíčová slova:

Anthrax – Antibiotics – Bacillus anthracis – Bacterial spores – Inhalation – Mouse models – Post-exposure prophylaxis – Prophylaxis


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