Improved antimicrobial efficacy with nitric oxide releasing nanoparticle generated S-nitrosoglutathione

S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology

“…22 In a similar study, NO-np were combined in solution with glutathione (GSH) to form nitrosoglutathione (GSNO) and demonstrated significantly improved antimicrobial activity against E. coli, indicating the important role of nitroso-intermediates in the eradication of Gram negative organisms. 12 Interestingly here, E. coli was inhibited to an even greater extent by SNO-CAP-np. The increased antimicrobial efficacy of SNO-CAP-np against E. coli may be attributable to improved SNO-CAP-mediated transnitrosylation activity, as opposed to free-formed GSNO by NO-np.…”

“…MRSA's defense against the antimicrobial effects of NO includes Hmp, 27 as well as NO-inducible lactate dehydrogenase, which facilitate maintenance of redox homeostasis in the presence of nitrosative stress. 28 While previous experiments demonstrated a significant difference in MRSA treated with NOreleasing therapy (NO-np) versus RSNO-generating therapy (NO-np + GSH), 12 the difference was not exceedingly pronounced, suggesting that both NO and RSNOs share equally important roles in the innate immune response.…”

“…12 However, at the bedside this would not be practical, as NO donation by the nanoparticles would form free GSNO, and in solution, both GSH and GSNO would decay to GSSG and become depleted. On the other hand, the SNO-CAP-np platform can release NO as well as facilitate transnitrosylation, thus providing a stable, long lasting reservoir of both NO and RSNO (SNO-CAP).…”

“…8 -11 We previously demonstrated that sustained generation of GSNO from a nitric oxide releasing nanoparticle platform (NO-np) in combination with solubilized GSH was highly effective against bacterial species in vivo (Pseudomonas aeruginosa) and in vitro (methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, P. aeruginosa, and Klebsiella pneumoniae). 12,13 Interestingly, when exposed to an aliquot of GSNO at the same concentration generated from the nanoparticles, no antibacterial activity was observed. 12 Thus, it is likely that sustained levels of GSNO generated by the nanoparticle platform are necessary for bactericidal activity.…”

“…12,13 Interestingly, when exposed to an aliquot of GSNO at the same concentration generated from the nanoparticles, no antibacterial activity was observed. 12 Thus, it is likely that sustained levels of GSNO generated by the nanoparticle platform are necessary for bactericidal activity.…”