Hypochlorous Acid as a Potential Wound Care Agent: Part II. Stabilized Hypochlorous Acid: Its Role in Decreasing Tissue Bacterial Bioburden and Overcoming the Inhibition of Infection on Wound Healing

Martin C Robson, Wyatt G Payne, Francis Ko, Marni Mentis, Guillermo Donati, Susan M Shafii, Susan Culverhouse, Lu Wang, Behzad Khosrovi, Ramin Najafi, Diane M Cooper, Mansour Bassiri, Martin C Robson, Wyatt G Payne, Francis Ko, Marni Mentis, Guillermo Donati, Susan M Shafii, Susan Culverhouse, Lu Wang, Behzad Khosrovi, Ramin Najafi, Diane M Cooper, Mansour Bassiri

Abstract

Background: A topical antimicrobial that can decrease the bacterial bioburden of chronic wounds without impairing the wound's ability to heal is a therapeutic imperative. A stabilized form of hypochlorous acid (NVC-101) has been demonstrated in vitro and in standard toxicity testing to possess properties that could fulfill these criteria. Materials and Methods: Using a standard rodent model of a chronically infected granulating wound, various preparations of NVC-101 and multiple treatment regimens were investigated to evaluate the role of NVC-101 in decreasing tissue bacterial bioburden and overcoming the inhibition of infection on wound healing. Quantitative bacteriology of tissue biopsies and wound healing trajectories were used to compare the various NVC-101 preparations and regimens to saline-treated negative controls and silver sulfadiazine-treated positive controls. Results: NVC-101 at 0.01% hypochlorous acid with a pH of 3.5 to 4.0 proved to be an effective topical antimicrobial. It was most effective when used for a brief period (15-30 minutes), and followed with another application. Possibly this was due to its rapid neutralization in the wound bed environment. Although not as effective at decreasing the tissue bacterial bioburden as silver sulfadiazine, NVC-101 was associated with improved wound closure. Conclusions: This stabilized form of hypochlorous acid (NVC-101) could have potential application as an antimicrobial wound irrigation and treatment solution if its effective pH range can be maintained in the clinical situation. NVC-101 solution was equally effective at pH 3.5 or 4.0 and more efficient soon after its application. As opposed to other antimicrobials investigated in this animal model, NVC-101 controls the tissue bacterial bioburden without inhibiting the wound healing process.

Figures

Figure 1
Figure 1
Depiction of the various groups in experiment 1 demonstrating the superiority of 30 minutes of NVC-101 application followed by another dressing for 23.5 hours over other regimens of hypochlorous acid. 1% silver sulfadiazine cream (Silvadene) was the most effective of all agents tested at decreasing the tissue bacterial bioburden.
Figure 2
Figure 2
Depiction of the various groups in experiment 2 demonstrating the superiority at decreasing bacterial counts of NVC-101 applied for 15 minutes, followed by gentle atraumatic wiping then 23.75 hours of a second dressing of NVC-101. There was essentially no difference in the effects with pH 3.5 and 4.0.
Figure 3
Figure 3
Wound healing trajectories from experiment 1, demonstrating faster healing for groups IV and IVb treated with a short application of NVC-101 followed by a second dressing of normal saline. These 2 groups had a more favorable wound healing trajectory than did group VIII treated with 1% silver sulfadiazine cream (Silvadene).
Figure 4
Figure 4
Wound healing trajectories from experiment 2, demonstrating the superiority of groups II and III, which consisted of a brief application of NVC-101, followed by gentle wiping, and a second application of NVC-101 over other regimens. The 2 groups with the fastest healing were also the most effective at controlling the tissue bacterial bioburden.

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