Pulmonary delivery of solid ciprofloxacin aerosol particles is an attractive possibility for chasing anthrax spores into the thoracic lymph nodes and killing the bacteria when the spores germinate. The overall goal of this project is to develop a method in which inhaled micron-sized particles of ciprofloxacin can be used to benefit victims of inhalational anthrax. We hypothesize that aerosol administered particles of Upophilic ciprofloxacin will be taken up by alveolar macrophages and transported to the thoracic lymph nodes where inhaled anthrax spores vegetate into active bacteria. Our strategy is intended to put the antibiotic at high and sustained concentrations within alveolar macrophages in lung and lymph locations. We anticipate that as the ciprofloxacin particles dissolve, the drug may be released within alveolar macrophages that contain or are near to other cells that contain spores, and be able to kill the bacteria when they germinate. Although several water-soluble antibiotics, including tobramycin, have been formulated for pulmonary delivery as inhaled aerosols, respirable particles of highly lipophilic antibiotics like ciprofloxacin have not, although others are examining the formation of liposomal ciprofloxacin. We have developed an effective method for aerosol delivery of lipophilic drugs based on the use of supercritical carbon dioxide as solvent and propellant. Our goals for this pilot project are to determine whether supercritical fluid drug aerosolization will allow inhalation delivery of ciprofloxacin to the lungs, to determine the uptake and dissolution properties of ciprofloxacin particles in cultured alveolar macrophages, to investigate ciprofloxacin particle translocation to the thoracic lymph nodes, and to determine the pharmacokinetic parameters. Our overall goal is to create a new tool for targeted treatment or prophylaxis for victims of anthrax spore inhalation.

R03AI061722

2004-09-30

2005-08-31