Spray-Dried Particles of Nitric Oxide-Modified Glutathione for the Treatment of Chronic Lung Infection.
Theerthankar DasHuai-Jin ChoongYee Chin KwangHak-Kim ChanJim ManosPhilip Chi Lip KwokHien T T DuongPublished in: Molecular pharmaceutics (2019)
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.
Keyphrases
- nitric oxide
- candida albicans
- pseudomonas aeruginosa
- staphylococcus aureus
- endothelial cells
- multidrug resistant
- biofilm formation
- healthcare
- high throughput
- pulmonary hypertension
- big data
- oxidative stress
- acinetobacter baumannii
- induced pluripotent stem cells
- cystic fibrosis
- drug resistant
- risk assessment
- machine learning
- escherichia coli
- health information
- combination therapy
- anti inflammatory
- replacement therapy
- smoking cessation