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.

Highlights

  • Since the discovery of penicillin in the 1920s followed by that of sulfonamides in the 1930s, many other antibiotics have been discovered, developed and commercially produced

  • In this paper we study the antimicrobial activity of IBU against Gram (+) and (−) species, against those pathogens involved in cystic fibrosis (CF), such as P. aeruginosa, methicillin resistant S. aureus and B. cepacia

  • We evaluated the effect of IBU-Na against other three bacterial species of particular interest in CF such as P. aeruginosa, S. aureus and B. cepacia

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Summary

Introduction

Since the discovery of penicillin in the 1920s followed by that of sulfonamides in the 1930s, many other antibiotics have been discovered, developed and commercially produced. Some innovative compounds are understudy, only a few new classes of antibiotics have been developed since the late 1980s. Compounds currently used for the treatment of non-infectious diseases as potential antimicrobial alternatives have been reviewed [12,13]. These compounds exert their antimicrobial activity through different mechanisms, affecting membrane, altering metabolism and intercalating DNA through the suppression of adhesion, among others [13].One example is Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug (NSAID) widely used for relief of pain, fever and inflammation, which has demonstrated microbicidal activity [14,15]

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