Bridging Phytomedicine and Nanotechnology: Novel Therapeutic Strategies for Diabetic Foot Ulcer Treatment

Abstract

Diabetic Foot Ulcers (DFUs) are the most severe and common complications of diabetes mellitus, which lead to morbidity, limb amputations, and increased healthcare costs. DFUs are pathophysiological complex conditions that typically involve varying degrees of neuropathy, ischemia, infection, oxidative stress, and chronic inflammation. Conventional treatments, such as offloading, debridement, antimicrobial therapy (topical or systemic), and dressings, often lead to a lengthy healing process, frequent recurrence, and growing concerns about antimicrobial resistance worldwide. This has led to considerable interest in phytoconstituents from traditional medicines for DFU management. Phytoconstituents with in-built anti-inflammatory, antioxidant, antimicrobial, and pro-angiogenic properties, like Curcuma longa, Aloe vera, Azadirachta indica, Centella asiatica, Berberis spp., and quercetin-containing plants, have demonstrated the capacity to heal wounds via alternative therapies, including their impact on specific cytokines, fibroblast activity, and collagen deposition. These agents, however, are not widely applicable for the management of DFU because they are poorly soluble, bioavailable, or stable. Nanotechnology-based delivery systems, such as nanoparticles, nano-emulsions, hydrogels, nanofibers, and solid lipid carriers, have the potential to improve targeted delivery and sustained release to the wound bed, thereby enabling agents to remain at the wound site. Recent work has shown improved outcomes with curcumin-loaded nanofibers and quercetin hydrogels for tissue regeneration, along with reduced infection rates. Despite some encouraging preclinical evidence, several regulatory hurdles, standardization challenges, and limited clinical evidence demonstrating DFU healing remain barriers to adoption in clinical practice.