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

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.

Anin silicoanalysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease

“…As mentioned above, there are evidences of benefits attributed to the inhalation of a hypertonic saline solution (HTS) in the treatment of patients with lung diseases. It has even been described beneficial effects on the bactericidal activity of ibuprofen against agents involved in the development of lung pathologies (Muñoz et al, 2018 ). Thus, we performed MD simulations to evaluate the influence of ionic strength (NaCl concentration) on the structure of the Ibuprofen–Mpro complexes.…”

“…One example is Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) widely used for relief of pain, fever and inflammation, which has demonstrated novel pharmacological actions against bacteria (Dai et al, 2019 ; Obad et al, 2015 ; Shah et al, 2018 ), fungi (Ogundeji et al, 2016 ; Sanyal et al, 1993 ) and viruses (Pan et al, 2018 ; Veljkovic et al, 2015 ). Interestingly, a short time ago, it was reported a nebulizable formulation of sodium Ibuprofen in high ionic strength with bactericidal properties for the treatment of respiratory infections of fibrotic patients (Muñoz et al, 2018 ). In addition to exhibiting antiviral properties.…”

Efficacy assessment of various natural and organic antimicrobials against Escherichia coli O157:H7, Salmonella enteritidis and Listeria monocytogenes

“…Lowering the pH signifies the effect of ibuprofen on L. monocytogenes and E. coli O157:H7. A recent study declared an enhanced effect of ibuprofen accompanied by sodium chloride (Muñoz et al 2018). Another study confirmed the anti-biofilm effect of ibuprofen against E. coli (Baldiris et al 2016).…”

Reversal of SARS-CoV2 Induced Hypoxia by Nebulized Sodium-Ibuprofen in a Compassionate Use Program

“…We have previously reported that sodium-ibuprofenate is a membrane penetrating amphiphatic molecule with antibacterial properties in the presence of hypertonic saline, rendering the combination bactericidal for Pseudomonas aeruginosa and Burkholderia cepacia (21).…”