Nitric Oxide Therapy for Dermatologic Disease

Figures & data

Figure 1.  Infected full-thickness dermal wounds on New Zealand white rabbit ears.

Ischemic (I) and nonischemic (N) wounds were treated with NO probiotic patch or control patch at days 1, 13, and 20 postsurgery.

gNO: Gaseous nitric oxide.

Reproduced with permission from [39]. © John Wiley & Sons, Inc. (2012).

Figure 2.  Methicillin-resistant Staphylococcus aureus-infected full-thickness wounds in mice at days 3 and 7: untreated, treated with empty nanoparticles and treated with nitric oxide nanoparticles.

NO: Nitric oxide; np: Nanoparticle.

Reproduced with permission from [46]. © Macmillan Publishers Ltd. (2009).

Figure 3.  Burn wounds infected with Candida albicans: untreated, treated with empty nanoparticles, and treated with nitric oxide nanoparticles, at days 0, 1, 5, 10 and 15.

Scale bar: 5 mm.

NO: Nitric oxide; np: Nanoparticle.

Reproduced with permission from [48]. © Macherla C, Sanchez DA, Ahmadi MS et al. (2012).

Figure 4.  Methicillin-resistant Staphylococcus aureus-infected murine abscesses: untreated, treated with empty nanoparticles, and treated with nitric oxide nanoparticles at day 4.

Arrows denote abscesses. Inset: representative purulent abscess 4 days post-methicillin-resistant Staphylococcus aureus infection. Scale bar: 5 mm.

NO: Nitric oxide; np: Nanoparticle.

Reproduced with permission from [49]. © Han et al. (2009).

Figure 5.  Pseudomonas aeruginosa-infected excisional wounds in mice: untreated, glutathione-treated, nitric oxide nanoparticle-treated and nitric oxide nanoparticle + glutathione-treated at days 1, 3 and 7.

Scale bar: 5 mm.

GSH: Glutathione; NO: Nitric oxide; np: Nanoparticle.

Reproduced with permission from [52]. © J. Drugs Dermatol. (2012).

Figure 6.  Role of reactive oxygen species in photoaging.

MMP: Matrix metalloproteinase; ROS: Reactive oxygen species.

Reprinted with permission from [57]. © Elsevier (2004).

Table 1.  Antimicrobial activities of nitric oxide-releasing platforms.

Platform	Advantages	Limitations	Active against
Acidified nitrite creams	Easily applied	Ingredients must be mixed immediately before application	Burkholderia cepacia
		Skin irritation	Mycobacterium ulcerans
			Propionibacterium acnes
			Pseudomonas aeruginosa
			Staphylococcus aureus (inc. MRSA)
			Tinea pedis
			Trichophyton spp.
Diazeniumdiolates (NONOates)	Easily produced	Risk of methemoglobin formation and release of toxic and carcinogenic byproducts	Candida albicans (DETA-NO)
	Stable under ambient conditions		Escherichia coli (β-Gal-NONOate)
	Spontaneous release of NO in predictable and dependable fashion
gNO	Little in vitro toxicity to human skin cells	Expensive	E. coli
		Difficult to handle	C. albicans
		Requires gas cylinders for delivery	P. aeruginosa
		Extended duration of treatment requiring nonambulation	S. aureus (inc. MRSA)
		Cannot be exposed to oxygen	Group B Streptococcus
		Potential host toxicity via NO2 production and methemoglobinemia development
NO-releasing nanoparticles (NO-np)	Ease of synthesis, storage, and administration		Acinetobacter baumannii
	Sustained NO retention and release		C. albicans
	Modifiable total NO quantity and rate of release		Enterococcus faecalis
	Minimal cutaneous and systemic toxicity		E. coli
			Klebsiella pneumoniae
			P. aeruginosa
			S. aureus (inc. MRSA)
			Staphylococcus epidermidis
			Trichophyton mentagrophytes
NO probiotic patch	Inexpensive	Patch-to-patch variability of gNO production depending on activity of Lactobacillus fermentum in each patch	A. baumannii
			E. coli
			P. aeruginosa
			S. aureus (inc. MRSA)
			T. mentagrophytes
			Trichophyton rubrum
Organic nitrates and nitrites (nitroglycerin, isosorbide mononitrate, sodium nitroprusside)	Long history of use	Limited knowledge of antimicrobial capabilities	Limited antibacterial properties
	Side effects well known	Tolerance development after prolonged use of nitrates
		Cyanide production by sodium nitroprusside
S-nitrosothiols (RSNOs)	Tissue selective	Require refrigeration in powder form prior to use	Acanthamoeba castellanii
	Can be designed to release NO at specified rates	Lack stability required for localized/topical delivery	Enterobacter aerogenes
			E. coli
			Leishmania spp.
			Plasmodium falciparum
			P. aeruginosa
			Coagulase-negative staphylococci
			Salmonella typhimurium
			Serratia marcescens
			S. aureus
			Trypanosoma cruzi
Zeolites (NO-metal complexes)	Stable	Lack of investigation into potential use in SSTI	Bacillus subtilis
	Modifiable NO release rate		Clostridium difficile
			E. coli
			P. aeruginosa
			S. aureus (inc. MRSA)

gNO: Gaseous nitric oxide; MRSA:Methicillin-resistant Staphylococcus aureus; NO: Nitric oxide; NONOate: Diazeniumdiolates; RSNO: Reactive nitrogen oxide species; SSTI: Skin and soft-tissue infection.

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