review · International Journal of Nanomedicine
Chronic diabetic wounds present significant clinical challenges because tissue healing mechanisms are disrupted. Hypoxia-inducible factor-1 alpha, or HIF-1α, plays a vital role in cellular responses to oxygen deprivation by promoting new blood vessel formation and tissue repair. In diabetic wounds, persistent hypoxia fails to trigger these responses because HIF-1α is destabilised and broken down by prolyl hydroxylase domain enzymes. While deferoxamine has traditionally been examined to stabilise HIF-1α, newer pharmacological options are emerging. These include novel prolyl hydroxylase domain inhibitors, such as roxadustat and daprodustat, alongside Von Hippel-Lindau protein antagonists. Because these agents currently see minimal use in wound healing, delivering them locally using advanced nanostructures offers a way to avoid systemic side effects, provide sustained release at the injury site, and enhance therapeutic outcomes.
Non-healing wounds are a major and debilitating complication for people living with diabetes. Restoring the body's natural response to tissue hypoxia could stimulate essential blood vessel growth and speed recovery. Delivering newer, targeted therapeutics using nanotechnology ensures the medicine acts precisely where needed, improving patient safety by avoiding widespread bodily exposure to the drugs.
This research outlines opportunities for pharmaceutical and medical device developers creating advanced topical wound dressings and localized therapeutics. By using nanostructures to deliver agents like roxadustat and daprodustat locally, developers could target diabetic foot ulcers and chronic sores. This remains early-stage concept work, as the abstract identifies this approach as a promising research gap with minimal current application in wound care.
AI-generated from the published abstract. Always read the original work before citing.
Chronic wounds in diabetic patients experience significant clinical challenges due to compromised healing processes. Hypoxia-inducible factor-1 alpha (HIF-1α) is a critical regulator in the cellular response to hypoxia, enhancing angiogenesis and tissue restoration. Nevertheless, the cellular response to the developed chronic hypoxia within diabetes is impaired, likely due to the destabilization of HIF-1α via degradation by prolyl hydroxylase domain (PHD) enzymes. Researchers have extensively explored HIF-1α activation as a potential pathway for diabetic wound management, focusing mainly on deferoxamine (DFO) as a potent agent to stabilize HIF-1α. This review provides an update of the other recent pharmacological agents managing HIF-1α activation, including novel PHD inhibitors (roxadustat and daprodustat) and Von Hippel-Lindau protein (VHL) antagonists, which could be potential alternatives for the local treatment of diabetic wounds. Furthermore, it highlights how localized delivery via advanced nanostructures can enhance the efficacy of these novel therapies. Importantly, by addressing these points, the current review can offer a promising area for research. Given that, these novel drugs have minimal applications in diabetic wound healing, particularly in the context of local application through nanomaterials. This gap presents an exciting opportunity for further investigation, as combining these drugs with localized nanotechnology could avoid undesired systemic side effects and sustain drug release within wound site, offering a transformative platform for diabetes wound treatment.
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DOI: 10.2147/ijn.s497041
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