KIU Publications

Chronic hyperglycemia in diabetes mellitus drives excessive reactive oxygen species (ROS) generation, mitochondrial dysfunction, advanced glycation end-product (AGE) formation, and persistent inflammation, collectively contributing to microvascular and macrovascular complications. Natural antioxidants including polyphenols, carotenoids, flavonoids, alkaloids, and terpenoids exert protective effects by scavenging ROS, activating endogenous antioxidant pathways, and modulating inflammatory signaling. However, their therapeutic translation is often limited by poor solubility, low oral bioavailability, rapid metabolism, and inadequate tissue targeting. Nanoencapsulation offers a promising strategy to overcome these barriers by improving stability, enhancing absorption, enabling sustained release, and facilitating targeted delivery to vulnerable organs such as kidney, retina, peripheral nerves, and cardiovascular tissues. Liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and nanogels have demonstrated enhanced pharmacokinetic and pharmacodynamic profiles of antioxidant compounds in preclinical models of diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. This review examines oxidative stress mechanisms in diabetic complications, the rationale for antioxidant nanoencapsulation, design strategies for organ-specific delivery, preclinical and emerging clinical evidence, safety considerations, and translational challenges. Nanoencapsulated natural antioxidants represent a compelling avenue for mitigating diabetesrelated tissue injury and advancing precision therapeutic interventions.