Antibacterial Efficacy of Exogenous Nitric Oxide on Periodontal Pathogens

Abstract

Current treatments for periodontitis (e.g., scaling/ root planing and chlorhexidine) have limited efficacy since they fail to suppress microbial biofilms satisfactorily over time, and the use of adjunctive antimicrobials can promote the emergence of antibiotic-resistant organisms. Herein, we report the novel application of nitric oxide (NO)-releasing scaffolds (i.e., dendrimers and silica particles) as anti-periodontopathogenic agents. The effectiveness of macromolecular NO release was demonstrated by a 3-log reduction in periodontopathogenic Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis viability. In contrast, Streptococcus mutans and Streptococcus sanguinis, caries-associated organisms, were substantially less sensitive to NO treatment. Both dendrimerand silica-based NO release exhibited substantially less toxicity to human gingival fibroblasts at concentrations necessary to eradicate periodontopathogens than did clinical concentrations of chlorhexidine. These results suggest the potential utility of macromolecular NO-release scaffolds as a novel platform for the development of periodontal disease therapeutics.

The Probiotic Lactobacillus fermentum Prevents Dysbiosis and Vascular Oxidative Stress in Rats with Hypertension Induced by Chronic Nitric Oxide Blockade

“…Prior works have demonstrated that dietary nitrate or exogenous NO exerts antimicrobial effects and can alter oral microbiome composition . However, dietary nitrates did not induced significant differences in fecal microbioma composition or diversity .…”

Anti-biofilm action of nitric oxide-releasing alkyl-modified poly(amidoamine) dendrimers against Streptococcus mutans

“…The reduced toxicity observed for NO-releasing long alkyl chain dendrimers, while maintaining superior anti-biofilm activity, demonstrates their potential utility as dental caries therapeutics. Indeed, the toxicity levels exhibited by the NO-releasing octyl- and dododecyl-modified dendrimers is comparable to that of clinical doses of chlorhexidine, which have been found to reduce HGF-1 cell viability by ~80% after 2 h [33]. …”

“…More recently, we reported on the controlled delivery of exogenous NO to kill S. mutans [32, 33]. In these studies, large instantaneous concentrations of NO were required to eradicate S. mutans .…”

Nitric Oxide–Releasing Macromolecular Scaffolds for Antibacterial Applications

“…For example, NO-releasing G1-PAMAM dendrimers exhibit stronger bactericidal action relative to silica nanoparticles of similar NO-release properties (attributable to enhanced bacterial-scaffold association of the dendritic scaffold). [87] However, the synthetic cost (e.g., synthesis and purification) of dendrimers is much greater than that of silica, with significant scale up and manufacturing hurdles. As a potential solution, Yang et al reported the synthesis of NO-releasing hyperbranched polymers via a one-pot reaction in bulk.…”