Topical Wound Treatment with a Nitric Oxide-Releasing PDE5 Inhibitor Formulation Enhances Blood Perfusion and Promotes Healing in Mice.
Maya Ben-Yehuda GreenwaldYu-Hang LiuWeiye LiPaul HiebertMaria ZubairHermann TenorTobias BraunReto NaefDaniel RazanskySabine WernerPublished in: Pharmaceutics (2022)
Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic.
Keyphrases
- wound healing
- nitric oxide
- label free
- drug delivery
- healthcare
- high fat diet induced
- high throughput
- public health
- mental health
- nitric oxide synthase
- hydrogen peroxide
- contrast enhanced
- drug induced
- machine learning
- type diabetes
- adipose tissue
- risk assessment
- computed tomography
- health information
- climate change
- social media
- combination therapy
- magnetic resonance
- adverse drug
- atomic force microscopy
- electronic health record
- replacement therapy