Protection of sildenafil citrate hydrogel against radiation-induced skin wounds

Radiation induced skin wound/dermatitis is one of the common side effects of radiotherapy or interventional radiobiology. In order to combat impaired healing of radiation wounds, alternative therapy to use sildenafil citrate (SC) topical hydrogel as a therapeutic option was proposed that has known to enhance nitric oxide in wounds. Our aim was to develop a radiation induced skin wound model and to investigate the wound healing efficacy of 5% SC hydrogel formulation in Sprague-Dawley rats. In the present study, the radiation wound inducing dose was optimized using a multi-dose localized γ-radiation trail with 10−55 Gy range (15 Gy interval). Optimal irradiation dose for wound induction was selected based on radiation skin damage assessment criteria followed the relative change from <35 Gy or>55 Gy showed significant variation and median 45 Gy γ-dose was selected for studying acute effects of radiation on wound healing. Significant (p < 0.05) higher wound contraction (88 ± 1.02%), skin damage reduction (81 ± 0.82%), tensile strength (45 ± 1.61%), nitric oxide and protein recovery (53 ± 0.72%) at dermal level prove the wound healing efficacy of 5% SC hydrogel formulation as compared to Rad 45 Gy control. In addition, the dose modifying factor (DMF) for SC hydrogel treatment was found to be 1.83 and 1.57 with respect to total wound area contraction and skin damage reduction. Skin histopathology in treated tissues showed improved granulation tissue formation, less inflammatory infiltrates and mature collagen fibres in the dermis. Thus, the modality could help to improve delayed wound healing in irradiated skin tissues.