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WIREs Nanomed Nanobiotechnol

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Use of nitric oxide nanoparticulate platform for the treatment of skin and soft tissue infections

Advanced Review

Allison J. Kutner, Adam J. Friedman

Published Online: May 09 2013

DOI: 10.1002/wnan.1230

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The incidence of skin and soft tissue infections (SSTI) due to multi‐drug resistant pathogens is increasing. The concomitant increase in antibiotic use along with the ease with which organisms develop mechanisms of resistance have together become a medical crisis, underscoring the importance of developing innovative and effective antimicrobial strategies. Nitric oxide (NO) is an endogenously produced molecule with many physiologic functions, including broad spectrum antimicrobial activity and immunomodulatory properties. The risk of resistance to NO is minimized because NO has multiple mechanisms of antimicrobial action. NO's clinical utility has been limited largely because it is highly reactive and lacks appropriate vehicles for storage and delivery. To harness NO's antimicrobial potential, a variety exogenous NO delivery platforms have been developed and evaluated, yet limitations preclude their use in the clinical setting. Nanotechnology represents a paradigm through which these limitations can be overcome, allowing for the encapsulation, controlled release, and focused delivery of NO for the treatment of SSTI. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1230 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Synthesis of nitric oxide (NO). Endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) calcium‐dependent, calmodulin‐regulated enzymes. They are constitutively expressed and catalyze the conversion of arginine to citrulline. Inducible NOS (iNOS) converts arginine to citrulline in a calcium‐independent fashion, and is activated by bacterial endotoxins and proinflammatory cytokines. (Reprinted with permission from Ref . Copyright 1998 Nature Publishing Group)

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Nitric oxide‐releasing nanoparticles (NO)‐nps decrease methicillin‐resistant Staphylococcus aureus (MRSA)‐infected intramuscular abscess area. Induced MRSA‐infected intramuscular abscesses were clinically evaluated on day 4 after infection. These images, untreated (a), treated with vancomycin (b), treated topically with NO‐nps (c), or treated intralesionally with NO‐nps (d) are representative of the clinical appearance of these lesions Arrows denote abscesses. (Reprinted with permission from Ref . Copyright 2012 Landes Bioscience)

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Nitric oxide‐releasing nanoparticles (NO‐nps) decrease methicillin‐resistant Staphylococcus aureus (MRSA)‐infected intradermal abscess area. Abscesses were untreated, treated with nanoparticles without NO (np), or treated with NO‐np, day 4. Arrows denote abscesses; inset demonstrates a representative purulent abscess 4 days after MRSA infection. Bar = 5 mm. (Reprinted with permission from Ref . Copyright 2009 Public Library of Science)

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Nitric oxide‐releasing nanoparticles (NO‐nps) accelerated healing in Candida albicans‐infected burn wounds. Wounds were untreated, treated with nanoparticles without NO (np), or treated with NO‐np. Bar = 5 mm. (Reprinted with permission from Ref . Copyright 2012 Frontiers)

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Nitric oxide‐releasing nanoparticles (NO‐nps) accelerated healing in Acinetobacter baumannii‐infected excisional wounds. Wounds were untreated, treated with nanoparticles without NO (np), or treated with NO‐np, 3 days post‐infection. (Reprinted with permission from Ref . Copyright 2010 Landes Bioscience)

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Nitric oxide‐releasing nanoparticles (NO‐nps) accelerated healing in methicillin‐resistant Staphylococcus aureus (MRSA)‐infected excisional wounds. Wounds were untreated, treated with nanoparticles without NO (np), or treated with NO‐np. (Reprinted with permission from Ref . Copyright 2009 Nature Publishing Group)

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(a) S‐nitrosoglutathione (GSNO) structure and (b) S‐nitroso‐N‐acetylcysteine (SNAC) structure. (Reprinted with permission from Ref . Copyright 2004 Wiley‐Blackwell)

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