M_2026_Artif.Cells.Nanomed.Biotechnol_54_53

Ascorbic acid (AA) has strong antioxidant and anti-diabetic activities; nevertheless, its therapeutic value is restricted due to rapid degradation, low-bioavailability and short systemic retention. To address these constraints, this study describes the development of a green-synthesized zinc oxide nanoparticle (ZnO NP)-based delivery system functionalized with AA (ZnO-AA NPs) and assesses its antidiabetic and neuroprotective effects. AA-assisted precipitation method was used to develop ZnO-AA NPs, which were then characterized by dynamic light scattering (DLS), zeta potential (ZP), scanning electron microscopy (SEM), FTIR spectroscopy and X-ray diffraction (XRD). The nanoparticles had a homogeneous size (-38 nm), good colloidal stability and a crystalline wurtzite structure. In vitro, ZnO-AA NPs showed dose-dependent inhibition of alpha-amylase and alpha-glucosidase. In vivo, oral ZnO-AA NPs (25 and 50 mg/kg) significantly improved glycaemic control, lipid profile and antioxidant enzyme levels compared to free AA (*p* < 0.01, *p* < 0.001; one-way/two-way ANOVA). ZnO-AA NPs dramatically reduced diabetes-related cognitive impairment, resulting in improved performance in the Morris water maze (MWM) and open field tests (OFTs) (*p* < 0.001), decreased hippocampal acetylcholinesterase (AChE) activity and preserved neuronal architecture. Overall, the ZnO-AA nanoformulation represents a multifunctional nanomedicine technique that improves the therapeutic efficacy of AA and has considerable promise for the treatment of diabetes and its associated neurodegenerative consequences.