Spray-Dried Particles of Nitric Oxide-Modified Glutathione for the Treatment of Chronic Lung Infection

Mol Pharm. 2019 Apr 1;16(4):1723-1731. doi: 10.1021/acs.molpharmaceut.9b00080. Epub 2019 Feb 22.

Abstract

Antibiotic resistance in pathogenic bacteria has emerged as a big challenge to human and animal health and significant economy loss worldwide. Development of novel strategies to tackle antibiotic resistance is of the utmost priority. In this study, we combined glutathione (GSH), a master antioxidant in all mammalian cells, and nitric oxide, a proven biofilm-dispersing agent, to produce GSNO. The resazurin biofilm viability assay, crystal violet biofilm assay, and confocal microscopy techniques showed that GSNO disrupted biofilms of both P. aeruginosa PAO1 and multidrug resistant A. baumaunii (MRAB 015069) more efficiently than GSH alone. In addition, GSNO showed a higher reduction in biofilm viability and biomass when combined with antibiotics. This combination treatment also inhibited A. baumaunii (MRAB 015069) growth and facilitated human foreskin fibroblast (HFF-1) confluence and growth simultaneously. A potentially inhalable GSNO powder with reasonable aerosol performance and antibiofilm activity was produced by spray drying. This combination shows promise as a novel formulation for treating pulmonary bacterial infections.

Keywords: S-nitrosoglutathione; aerosol; antibiotic resistance; biofilm; glutathione; lung infection; nitric oxide; spray drying.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Biofilms / growth & development*
  • Chronic Disease
  • Drug Compounding
  • Dry Powder Inhalers / methods*
  • Fibroblasts / drug effects
  • Fibroblasts / microbiology
  • Glutathione / chemistry*
  • Humans
  • Lung / drug effects*
  • Lung / microbiology
  • Nitric Oxide / chemistry*
  • Pseudomonas aeruginosa / drug effects
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Nitric Oxide
  • Glutathione