Abstract
ABSTRACTDimethyl sulfoxide (DMSO) and polyethylene glycols (PEGs) are frequently used as potent excipients in pharmaceutical formulations. However, these agents also have an interesting antimicrobial and anti-inflammatory profile that could interfere with the efficacy testing of anti-infective compounds when the latter are solubilized in DMSO or PEGs. Here, we demonstrate the antimicrobial and anti-inflammatory effects of DMSO-PEG400 in a murine Pseudomonas aeruginosa infection model, aiming to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infectives.IMPORTANCE Our study demonstrates the antimicrobial and anti-inflammatory effects of the combination of DMSO and PEG400 against Pseudomonas aeruginosa in vitro and in vivo in a murine infection model of heightened intestinal permeability. The aim of this study is to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infective compounds, to avoid interference with the assay or system tested. This is an extremely important consideration, since potential antimicrobial and anti-inflammatory effects of the solvent vehicle are detrimental to research studies on the efficacy of new anti-infective agents, given that the vehicle effect can mask the effect of the tested compounds. Our results can therefore be of great value to the scientific community, as they can guide researchers in the future to avoid this significant pitfall that can cost substantial amounts of money and valuable time during investigations of the effects of novel, difficult-to-solubilize antimicrobial compounds.
Highlights
Dimethyl sulfoxide (DMSO) and polyethylene glycols (PEGs) are frequently used as potent excipients in pharmaceutical formulations
DMSO has been suggested to exert its antimicrobial effects as a result of bacterial membrane penetration and perturbation [13, 14], while PEGs are thought to lead to bacterial cell clumps and microbial morphological alterations that eventually lead to bacterial killing [7]
To solubilize these novel compounds, we used a combination of DMSO and PEG400 to assess their effects in a clinically relevant murine Pseudomonas aeruginosa (PA) infection model
Summary
Dimethyl sulfoxide (DMSO) and polyethylene glycols (PEGs) are frequently used as potent excipients in pharmaceutical formulations These agents have an interesting antimicrobial and anti-inflammatory profile that could interfere with the efficacy testing of anti-infective compounds when the latter are solubilized in DMSO or PEGs. Here, we demonstrate the antimicrobial and anti-inflammatory effects of DMSO-PEG400 in a murine Pseudomonas aeruginosa infection model, aiming to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infectives. Our group has developed a new family of antimicrobial compounds against Pseudomonas aeruginosa (PA) that target bacterial virulence [15,16,17,18,19] To solubilize these novel compounds, we used a combination of DMSO and PEG400 to assess their effects in a clinically relevant murine PA infection model. We aimed to demonstrate the DMSO-PEG400 antimicrobial and anti-inflammatory effects in vivo and draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infective compounds to avoid interference with the assay or system tested
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