BACKGROUND: Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half-life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle-based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects. METHODS: Porous organosilica microparticles (SNO-MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO-MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO-MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one-way analysis of variance with Bonferroni correction. RESULTS: SNO-MP displayed antibacterial activity against gram-positive (methicillin-resistant and -sensitive Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO-MP induced dose-dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO-MP (10 mg/mL) induced a 99.99%-100% reduction in CFU across all isolates, equivalent to a 5-9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles. CONCLUSION: SNO-MP demonstrates potent bactericidal effect against antibiotic-resistant CRS bacterial strains.
BACKGROUND: Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half-life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle-based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects. METHODS: Porous organosilica microparticles (SNO-MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO-MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO-MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one-way analysis of variance with Bonferroni correction. RESULTS:SNO-MP displayed antibacterial activity against gram-positive (methicillin-resistant and -sensitive Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO-MP induced dose-dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO-MP (10 mg/mL) induced a 99.99%-100% reduction in CFU across all isolates, equivalent to a 5-9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles. CONCLUSION:SNO-MP demonstrates potent bactericidal effect against antibiotic-resistant CRS bacterial strains.
Authors: Levi G Cleare; Kevin L Li; Waleed M Abuzeid; Parimala Nacharaju; Joel M Friedman; Joshua D Nosanchuk Journal: J Fungi (Basel) Date: 2020-06-12