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Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax
Chad W Stratilo1, Scott Jager1, Melissa Crichton1
1Bio Threat Defence Section, Suffield Research Centre, Defence Research and Development Canada, Ralston, Alberta, Canada.
Abstract:
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.
Insights
Liposomal ciprofloxacin formulations, Lipoquin and Apulmiq, show high efficacy against anthrax (Bacillus anthracis) in mice. These treatments offer promising post-exposure prophylaxis and therapeutic options for inhalational anthrax.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Delivery Systems
Background:
- Anthrax, caused by Bacillus anthracis, poses a significant bioterrorism threat.
- Current anthrax treatments require frequent dosing and can have systemic side effects.
- Liposomal drug delivery offers potential for improved therapeutic profiles, including targeted delivery and reduced systemic exposure.
Purpose of the Study:
- To evaluate the in vivo efficacy of two liposomal ciprofloxacin formulations, Lipoquin and Apulmiq, against Bacillus anthracis.
- To assess the effectiveness of these formulations in post-exposure prophylaxis (PEP) and delayed treatment models of inhalational anthrax in mice.
- To determine optimal dosing schedules and therapeutic windows for liposomal ciprofloxacin.
Main Methods:
- Murine model of inhalational anthrax.
- Administration of Lipoquin and Apulmiq via intranasal instillation.
- Evaluation of different doses and treatment schedules (early vs. delayed post-exposure).
- Comparison of survival rates between treatment groups and vehicle control.
Main Results:
- All treatment groups showed significantly improved survival compared to the vehicle control.
- Lipoquin and Apulmiq provided 87-90% protection when administered within 24 hours of exposure for 7 days.
- Even with a reduced 3-day therapy course within 24 hours of exposure, protection ranged from 60-87%.
- Delayed treatment (48 hours post-exposure) resulted in reduced survival rates of 46-65%.
Conclusions:
- Liposomal encapsulated ciprofloxacin (Lipoquin and Apulmiq) demonstrates significant efficacy in treating and preventing inhalational anthrax in a murine model.
- Intranasal delivery of these formulations allows for targeted delivery and potentially reduced systemic side effects.
- These liposomal formulations represent promising candidates for post-exposure prophylaxis and as part of combination therapies for Bacillus anthracis infections.
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