Department of Surgery, Harvard Medical School and Massachusetts General Hospitalgrid.32224.35, Boston, Massachusetts, USA.
Shriners Hospitals for Children Boston, Boston, Massachusetts, USA.
Microbiol Spectr. 2021 Sep 3;9(1):e0023321. doi: 10.1128/Spectrum.00233-21. Epub 2021 Aug 4.
Dimethyl 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. Our study demonstrates the antimicrobial and anti-inflammatory effects of the combination of DMSO and PEG400 against Pseudomonas aeruginosa and 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.
二甲基亚砜(DMSO)和聚乙二醇(PEG)经常被用作药物制剂中的有效赋形剂。然而,这些试剂也具有有趣的抗菌和抗炎特性,如果将抗感染化合物溶解在 DMSO 或 PEG 中,可能会干扰其疗效测试。在这里,我们在铜绿假单胞菌感染模型中证明了 DMSO-PEG400 的抗菌和抗炎作用,旨在引起人们对难以溶解的抗感染药物选择合适溶剂的关注。
我们的研究表明,DMSO 和 PEG400 的组合对铜绿假单胞菌具有抗菌和抗炎作用,并且在肠道通透性增加的小鼠感染模型中也具有这种作用。本研究的目的是引起人们对难以溶解的抗感染化合物的溶剂选择的关注,以避免对测定或测试系统产生干扰。这是一个极其重要的考虑因素,因为溶剂载体的潜在抗菌和抗炎作用会损害新抗感染药物疗效的研究,因为载体效应会掩盖测试化合物的作用。因此,我们的研究结果对于科学界具有重要价值,因为它们可以指导未来的研究人员避免这种重大陷阱,这可能会在研究新型、难以溶解的抗菌化合物的效果时花费大量的金钱和宝贵的时间。