Nanoparticle-Mediated Quercetin Delivery Mitigates Oxidative Stress in Diabetic Neuropathy in Experimental Animals

Diabetic neuropathy is an ascending neurodegenerative condition of diabetes mellitus, which is heralded by sensory dysfunction, motor disability, and chronic neuropathic pain largely due to oxidative stress and mitochondrial impairment caused by hyperglycemia. Quercetin, a naturally occurring flavonoid, exhibits strong antioxidant and neuroprotective effects; however, its clinical application is limited by its low water solubility, poor bioavailability, and short half-life. The focus of the current study was to formulate and optimise quercetin-loaded polymeric nanoparticles and to investigate their efficacy in the treatment of diabetic neuropathy using an experimental animal model. Nanoparticles of quercetin were prepared by employing the solvent evaporation method, yielding 10 formulations (F1–F10) with different drug: polymer ratios. All-round physicochemical characterisation indicated F5 as an optimised system with a minimum particle size (182.3 ± 4.8 nm), maximum encapsulation efficiency (89.6 ± 2.1%), appropriate zeta potential (−31.7 ± 1.4 mV) and a sustainable in-vitro drug release profile. In-vitro antioxidant tests showed that the free radical activity of F5 was significantly improved compared to that of quercetin. In streptozotocin-induced diabetic rats, F5 significantly improved behavioural changes, suppressed oxidative stress, and restored the endogenous antioxidant defence mechanism and the morphology of the peripheral nerve. Overall, these results suggest that nanoparticle-mediated delivery of quercetin significantly enhances its neuroprotective efficacy and provides a promising treatment for diabetic neuropathy.