Nitric oxide-releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates

Waleed M. Abuzeid, Vallerinteavide Mavelli Girish, Judd H. Fastenberg, Andrew R. Draganski, Andrew Y. Lee, Joshua D. Nosanchuk, Joel M. Friedman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1190-1198
Number of pages9
JournalInternational Forum of Allergy and Rhinology
Volume8
Issue number10
DOIs
StatePublished - Oct 1 2018

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Nitric Oxide
Stem Cells
Colony-Forming Units Assay
Enterobacter aerogenes
Proteus mirabilis
Immunologic Factors
Therapeutics
Methicillin-Resistant Staphylococcus aureus
Biofilms
Microbial Drug Resistance
Body Temperature
Sulfhydryl Compounds
Nanoparticles
Pseudomonas aeruginosa
Agar
Half-Life
Suspensions
Analysis of Variance
Anti-Bacterial Agents
Bacteria

Keywords

  • bacteriology
  • biofilm
  • chronic rhinosinusitis
  • Therapeutics
  • topical therapy for chronic rhinosinusitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

Cite this

Nitric oxide-releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates. / Abuzeid, Waleed M.; Girish, Vallerinteavide Mavelli; Fastenberg, Judd H.; Draganski, Andrew R.; Lee, Andrew Y.; Nosanchuk, Joshua D.; Friedman, Joel M.

In: International Forum of Allergy and Rhinology, Vol. 8, No. 10, 01.10.2018, p. 1190-1198.

Research output: Contribution to journalArticle

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abstract = "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.",
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author = "Abuzeid, {Waleed M.} and Girish, {Vallerinteavide Mavelli} and Fastenberg, {Judd H.} and Draganski, {Andrew R.} and Lee, {Andrew Y.} and Nosanchuk, {Joshua D.} and Friedman, {Joel M.}",
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AU - Abuzeid, Waleed M.

AU - Girish, Vallerinteavide Mavelli

AU - Fastenberg, Judd H.

AU - Draganski, Andrew R.

AU - Lee, Andrew Y.

AU - Nosanchuk, Joshua D.

AU - Friedman, Joel M.

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N2 - 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.

AB - 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.

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KW - topical therapy for chronic rhinosinusitis

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