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Pharmaceuticals 2018, 11(2), 47; https://doi.org/10.3390/ph11020047

High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens

1
Centro de Excelencia en Productos y Procesos de Córdoba, Gobierno de la Provincia de Córdoba, Pabellón CEPROCOR, Santa María de Punilla, Córdoba CP 5164, Argentina
2
Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Godoy Cruz 2290, C1425FQB CABA, Argentina
3
Instituto de Investigaciones en Ciencias de la Salud—FCM (INICSA-CONICET), Córdoba C 5000, Argentina
4
Departamento de Salud y Educación Cátedra de Patología, Universidad Nacional de La Rioja, La Rioja C 5300, Argentina
5
Cátedra de Patología, Universidad Nacional de Córdoba, Córdoba C 5000, Argentina
6
Cátedra de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba C 5000, Argentina
*
Authors to whom correspondence should be addressed.
Received: 16 February 2018 / Revised: 4 April 2018 / Accepted: 5 April 2018 / Published: 17 May 2018
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Abstract

Ibuprofen (IBU-H), a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa, methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na) and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes. In short time periods, where neither IBU-Na nor controls with 1 M NaCl show activity, the combination of both leads to a reduction in the bacterial load. We also analyzed whether the changes caused by salt on the bacterial membrane also promoted the activity of other microbicide compounds used in cystic fibrosis like gentamicin, tobramycin and phosphomycin. The results show that the presence of ionic strength only enhanced the bactericidal activity of the amphipathic molecule of IBU-Na. In this respect, the effect of saline concentration was also reflected in the surface properties of IBU-Na, where, in addition to the clear differences observed between 145 mM and 1 M, singular behaviors were also found, different in each condition. The combination of anti-inflammatory activity and this improved bactericidal effect of Na-IBU in hypertonic solution provides a new alternative for the treatment of respiratory infections of fibrotic patients based on known and widely used compounds. View Full-Text
Keywords: ibuprofen; P. aeruginosa; cystic fibrosis; bactericide activity; synergy ibuprofen; P. aeruginosa; cystic fibrosis; bactericide activity; synergy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Muñoz, A.J.; Alasino, R.V.; Garro, A.G.; Heredia, V.; García, N.H.; Cremonezzi, D.C.; Beltramo, D.M. High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens. Pharmaceuticals 2018, 11, 47.

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