Biofilms caused by the bacteria Pseudomonas aeruginosa are a leading cause of persistent lung infections in patients who have chronic lung disease or are otherwise immunosuppressed. Mucoid strains of P. aeruginosa secrete polysaccharides to form an extracellular matrix which binds the bacteria together and protects them from antimicrobial agents and the patient's immune system. Because of this afforded protection by the biofilm matrix, current treatments are only minimally effective and result in alleviation of some symptoms but not a cure of the infection. Therefore, we are developing a new approach for the treatment of respiratory biofilms by combining a dispersion compound to break up bacterial colonies with antibiotics into a dry aerosol. These systems are aimed at enabling the use of traditional antibiotics for effective pathogen killing of biofilm-forming pathogens.

Inhalable dry powders have been formulated by spray drying aqueous solutions containing Ciprofloxacin HCl (antibiotic), glutamic acid (dispersion compound) and L-leucine (excipient). The effects of formulation and spray-drying process parameters on the aerodynamic diameter and chemical activity of the powder were examined using central composite design. Powder geometric diameter was determined by laser diffraction and particle density was estimated by tap density measurements. Powders were formulated with theoretical aerodynamic diameters, as estimated by the equation d_aero=d_geom√ρ, that ranged from 2-8 µm, appropriate for efficient deposition within the respiratory tract. The in vitro deposition profiles of the powders were evaluated using a Next Generation Impactor operated at 60 L/min. High deposition efficiencies (>40%) were observed for powders with optimized physical properties. Scanning electron microscopy showed that the particles have a collapsed spherical structure with a porous internal morphology. Powders were found to contain about 98% of the expected antibiotic load, indicating that the drug was not lost or harmed during the spray-drying process. Finally, the efficacy of the dry powder drug delivery system was tested on an in vitro respiratory biofilm model developed by culturing a mucoid producing strain of P. aeruginosa on Calu-3 human bronchial epithelial cells. Live/dead assay coupled with confocal microscopy showed that the drug delivery system was more effective at eliminating biofilms in vitro compared to traditional antibiotic treatment. This co-delivery system offers a new treatment strategy for bacterial biofilms which may improve the elimination of persistent infections in the lungs.