Antimicrobial Activity of Ibuprofen Against Cystic Fibrosis Associated Gram – Negative Pathogens

Author :Parth N. Shah, Kimberly R. Marshall-Batty, Justin A. Smolen, Jasur A. Tagaev, Qingquan Chen, Christopher A. Rodesney, Henry H. Le, Vernita D. Gordon, David E. Greenberg, Carolyn L. Cannon
Publisher :Antimicrobial Agents and Chemotherapy
Volume :62
Number :2
Year :2018
DOI: : 10.1128/AAC.01574-17

Clinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen’s anti-inflammatory properties. Yet, a few previous reports demonstrate an antimicrobial activity of ibuprofen as well, although none investigate its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen’s in vitro antimicrobial activity against Pseudomonas aeruginosa and Burkholderia spp. strains through measurements of endpoint colony-forming units (CFU) and growth kinetics showed that ibuprofen reduces the growth rate and bacterial burden of tested strains in a dose-dependent fashion. In an in vitro Pseudomonas biofilm model, a reduction in the rate of biomass accumulation over 8-h of growth with ibuprofen treatment was observed. Next, an acute Pseudomonas pneumonia model was used to test this antimicrobial activity after oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with control animals. Preliminary biodistribution studies performed after aerosolization of ibuprofen to mice demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulating polymeric nanoparticles (Ibu-NPs) were formulated to improve the pharmacokinetic profile. Ibu-NPs, formulated for aerosol delivery, inhibited the growth of P. aeruginosa in vitro and may provide a convenient dosing method. These results provide an additional explanation for the previously observed therapeutic effects of ibuprofen in CF patients, and further strengthen the argument for its use for these patients.