Spray with Nitric Oxide Donor Accelerates Wound Healing: Potential Off-the-Shelf Solution for Therapy?

BACKGROUND: Ditrosyl iron complexes (DNIC) are endogenous donors of nitric oxide. The possibility of their application to stimulate regeneration has been studied for more than 15 years. However, the most effective dose and form of delivery have not yet been determined. PURPOSE: The aim of this research was to develop a spray form of DNIC that accelerates wound healing. METHODS: We prepared a series of DNIC sprays with spray dosages of 10, 50 and 100 μg. We modelled full-thickness skin wounds in 24 Wistar rats and treated them with distilled water (n = 6), 10 (n = 6), 50 (n = 6) and 100 μg (n = 6) for three post-operative days. On the fourth day, the excised wound tissues were studied by morphological, immunohistochemical and morphometric methods. RESULTS: We demonstrated that 50 μg of DNIC spray had the most beneficial effect on wound healing: the thickness of the granulation tissue layer was 140% higher, vimentin positive fibroblasts predominated and the intensity of inflammation was significantly lower than in the control. There was a dose-dependent decrease in the functional activity of mast cells in the experimental groups compared to the control. CONCLUSION: DNIC spray is a potential effective dosage form for the treatment of large-area skin lesions.