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

Abstract

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.

Winner of the society for biomaterials young investigator award for the annual meeting of the society for biomaterials, April 11–14, 2018, Atlanta, GA: S‐nitrosated poly(propylene sulfide) nanoparticles for enhanced nitric oxide delivery to lymphatic tissues

“…Despite the highly reactive and potentially cytotoxic nature of NO, we observed histologically no signs of inflammation at the site of SNO‐NP injection, as either changes in skin thickness or granularity [Fig. (A)], which is in line with several studies reporting the lack of inflammatory effects from NO donors . Additionally, no increases in ONOO ‐ were detected in any assayed tissue [Fig.…”

Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm Formation In Vitro and in a Rodent Central Venous Catheter Model

“…Instead, the platform facilitates the reduction of encapsulated nitrite salt to NO through a stable dinitrogen trioxide intermediate, which, upon exposure to water, generates NO. Therefore, NO-np are rather true NO generators instead of donors like many of the aforementioned chemical entities (41). Additionally, we have demonstrated in vitro that NO-np show minimal toxicity toward cultured human lung fibroblasts (23).…”

Nitric Oxide Therapy for Dermatologic Disease

“…NOS2/inducible NOS (iNOS), on the other hand, generates large quantities of NO by a noncalcium-dependent mechanism. It is stimulated by bacterial products, cytokines and neuropeptides [1,2]. …”

“…Peroxynitrite (OONO - ), the most reactive and cytotoxic RNOS, forms when NO interacts with superoxide. RNOS possess numerous antimicrobial properties, including: Induction of nitrosative and oxidative stress;Inactivation of essential enzymes;Depletion of intracellular iron stores;Damage to microbial DNA, directly and indirectly (via generation of alkylating agents and hydrogen peroxide and inhibition of DNA repair);Disruption of the microbial cell membrane through lipid peroxidation [2,19–20]. …”

“…Although these systems are discussed at length in other articles in this issue, Table 1 lists the major classes of agents tested for antimicrobial capability along with their strengths and weaknesses and the organisms against which they have shown activity. Taken in sum, the various NO-releasing technologies demonstrate NO's activity against an impressive array of organisms, including Gram-positive and -negative bacteria, fungi and parasites [2,19,24]. …”