Anti-microbial Efficacy of Silicone-based Nitric Oxide- releasing Wound Dressings in a Dermal Porcine Wound Model

Introduction: Nitric oxide (NO) is a short-lived, diatomic, lipophil- ic gas with antimicrobial activity. Several in-vitro and in-vivo studies have demonstrated the efficacy of NO in microbial reduction. Recent- ly, NO and its derivatives have been shown to exhibit broad-spectrum antimicrobial activity against bacteria, viruses, and parasites. The ob- jective of this study was to assess the efficacy of various topical PDMS (silicone)-based nitric oxide formulations on microbial reduction and healing using a porcine wound model. A NO donor (SNAP; S-nitro- so-N-acetylpenicillamine) was utilized to continually release NO gas from the PDMS film to the wound surface. Methods: Thirty-three (33) deep reticular dermal wounds (22mm x 22mm x 3mm deep) were made with a specialized electrokeratome in 4 animals. Methicillin Resistant Staphylococcus aureus USA300 (MRSA USA300) or Pseudomonas aeruginosa PA 090-010 (PA: mil- itary isolation) were inoculated in 2 animals per organism. After 24 hours, the dressings were removed, and three wounds were recovered for baseline enumeration. Wounds were randomly assigned to one of the following treatment groups: A- NO donor loaded at 10 wt%, B- PDMS Vehicle Control, C- Silver Sulfadiazine Positive Control and D- Untreated Control. Wounds were recovered on days 7 and 12 and assessed for bacterial burden and wound healing. Results: Significant reductions (p ≤ 0.05) were observed in wounds treated with NO donor 10 wt% infected either with MRSA USA300 or PA09-010, compared to baseline and untreated control. Wounds treated with the NO donor 10 wt% demonstrated a 99.8% reduction of MRSA compared with untreated wounds. In wounds infected with PA09-010 reductions exhibited values of 93.7% compared to untreated control. In wounds infected with MRSA USA300 and treated with NO donor 10 wt%, significant reductions (p ≤ 0.05) were also observed against PDMS Vehicle Control and Silver Sulfadiazine. No detrimental effects on wound healing were observed by NO donor loaded PDMS films at 10 wt%. Discussion: NO rapidly decreased wound bacterial count signifi- cantly, suggesting an important advance in the treatment of infected wounds. These studies may have important clinical implications in eradication of bacteria in open wounds with topically applied nitric oxide (NO)-releasing wound dressings.