Investigating the effect of tobramycin dry powder inhaler on the eradication of Pseudomonas aeruginosa biofilms

Biofilms are sessile communities of microorganisms embedded within a self-generated extracellular polymeric matrix, which consists of polysaccharides, DNA, and/or proteins. Such biofilms are found for instance in adults with cystic fibrosis, with pulmonary infections with the Gram-negative bacterium Pseudomonas aeruginosa being particularly common and responsible for a high mortality rate among CF patients. This infection in CF patients is commonly managed with antibiotic dry powder inhalers, one of which is the aminoglycoside tobramycin. The activity of tobramycin has been well characterized in vitro, but current models that have been used are not very representative for lung infections, and better models would provide a significant advantage as these could be used, for instance, to improve the formulation of dry powder inhalers.
For instance, one question that has not been addressed with current models is whether the size of drug particles emitted from a dry powder inhaler influences the efficacy of the anti-biofilm activity of the antibiotic. In this project, we utilized the Next Generation Impactor (NGI), which is a pharmaceutical instrument used to separate particles into size fractions. We used the NGI to separate tobramycin particles into different sizes and tested the influence of these particles on eradication of P. aeruginosa biofilms, which were grown using as colony biofilms that closely mimics conditions in the lung where biofilms are grown on a substrate-air interface. Preliminary evidence indicated smaller tobramycin particles are better in eradication of P. aeruginosa biofilms as compared to larger particles. Our results may represent a step towards improving the formulation of tobramycin dry powder inhalers to be effective in eradicating P. aeruginosa biofilms.