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Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens
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 demonstrated an antimicrobial activity of ibuprofen as well, although none invest...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826130/ https://www.ncbi.nlm.nih.gov/pubmed/29311081 http://dx.doi.org/10.1128/AAC.01574-17 |
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author | Shah, Parth N. Marshall-Batty, Kimberly R. Smolen, Justin A. Tagaev, Jasur A. Chen, Qingquan Rodesney, Christopher A. Le, Henry H. Gordon, Vernita D. Greenberg, David E. Cannon, Carolyn L. |
author_facet | Shah, Parth N. Marshall-Batty, Kimberly R. Smolen, Justin A. Tagaev, Jasur A. Chen, Qingquan Rodesney, Christopher A. Le, Henry H. Gordon, Vernita D. Greenberg, David E. Cannon, Carolyn L. |
author_sort | Shah, Parth N. |
collection | PubMed |
description | 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 demonstrated an antimicrobial activity of ibuprofen as well, although none investigated 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 species strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the 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 the oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with the control animals. Preliminary biodistribution studies performed after the delivery of ibuprofen to mice by aerosol demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulated 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 by these patients. |
format | Online Article Text |
id | pubmed-5826130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-58261302018-08-23 Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens Shah, Parth N. Marshall-Batty, Kimberly R. Smolen, Justin A. Tagaev, Jasur A. Chen, Qingquan Rodesney, Christopher A. Le, Henry H. Gordon, Vernita D. Greenberg, David E. Cannon, Carolyn L. Antimicrob Agents Chemother Experimental Therapeutics 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 demonstrated an antimicrobial activity of ibuprofen as well, although none investigated 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 species strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the 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 the oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with the control animals. Preliminary biodistribution studies performed after the delivery of ibuprofen to mice by aerosol demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulated 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 by these patients. American Society for Microbiology 2018-02-23 /pmc/articles/PMC5826130/ /pubmed/29311081 http://dx.doi.org/10.1128/AAC.01574-17 Text en Copyright © 2018 Shah et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Experimental Therapeutics Shah, Parth N. Marshall-Batty, Kimberly R. Smolen, Justin A. Tagaev, Jasur A. Chen, Qingquan Rodesney, Christopher A. Le, Henry H. Gordon, Vernita D. Greenberg, David E. Cannon, Carolyn L. Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title | Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title_full | Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title_fullStr | Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title_full_unstemmed | Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title_short | Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens |
title_sort | antimicrobial activity of ibuprofen against cystic fibrosis-associated gram-negative pathogens |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826130/ https://www.ncbi.nlm.nih.gov/pubmed/29311081 http://dx.doi.org/10.1128/AAC.01574-17 |
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