Aerosol delivery of liposome-encapsulated ciprofloxacin: Aerosol characterization and efficacy against Francisella tularensis infection in mice

Abstract

The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12 commercially available jet nebulizers was evaluated in this study. Aerosol particles containing liposome-encapsulated ciprofloxacin generated by the nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were determined, and the drug contents of the sampling filters from each run onto which aerosolized liposome-encapsulated ciprofloxacin had been deposited were analyzed spectrophotometrically. The aerosol particles of liposome- encapsulated ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 μm, with GSDs ranging from 1.51 to 1.84 μm. The drug contents of the sampling filters exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from 12.7 to 40.5 μg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected on the basis of most desirable MMADs, particle counts, and drug deposition, aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of mice infected with 10 times the 50% lethal dose of Francisella tularensis. All mice treated with aerosolized liposome- encapsulated ciprofloxacin survived the infection, while all ciprofloxacin- treated or untreated control mice succumbed to the infection (P < 0.001). These results suggest that aerosol delivery of liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible and that it may provide an effective therapy for the treatment of respiratory tract infections.