Smart Nanoplatforms for Plant derived Bioactive-Based Diabetic Wound Healing: Trends, Challenges, and Breakthroughs

Diabetic wounds pose a major global health burden, it is characterized by impaired healing, chronic inflammation and high fatality rate for infections. Novel therapeutic opportunities are arising by the combination of nanotechnology and bioactive compounds from plants. This review discusses the latest developments of smart nanoplatforms for delivering plant-derived bioactives, their potential mechanisms in the treatment of diabetic wounds, and the current and prospects of their clinical and translation practice. A literature search was performed focusing on preclinical and clinical studies about polymeric, lipid based and metal nanoparticle systems loaded with phytoconstituents. Action mechanisms, delivery efficiencies, and therapeutic results were thoroughly reviewed. Stimuli-responsive systems, bioactive scaffolds, and integrated biosensors received particularly attention. Nanoplatformbased phytosomes, nanofibers, and lipid-based carriers have greatly improved the stability, solubility, and targeted delivery of plant bioactives such as curcumin, quercetin, and asiaticoside. These systems modified the oxidative stress, suppressed pro-inflammatory cytokines and promoted angiogenesis and re-epithelialization. The introduction of biosensors and gene-loaded nanoparticles increased the efficacy of therapy. In animal models, faster wounds closure, increased collagen deposit, and reduced microbial load have been shown. The smart nano-delivery systems based on plant bioactives exhibit a promising impact in diabetic wound management providing a platform to overcome the various pathological barriers associated with this disease. Further refinements in the design of nanocarrier, incorporation of bio-sensing technologies and rigorous clinical validation are required to translate these promising platforms into routine wound therapy.