eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-04-27 19 2 71553 article Yallamalli Indira Muzib 1 Chella Shilpaja 1 Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati Alzheimer’s disease (AD) is a chronic neurodegenerative condition characterized by progressive memory loss and cognitive dysfunction. Although donepezil (DPZ), an acetylcholinesterase inhibitor, is frequently prescribed to manage AD symptoms, its effectiveness is hindered by limited brain penetration due to the blood-brain barrier (BBB) and extensive first-pass metabolism. This research focused on formulating a nanoemulsion (DPZ-NE) for intranasal delivery to improve brain targeting and therapeutic outcomes. A pseudo-ternary phase diagram was developed to determine the optimal composition, using oleic acid as the oil phase, PEG 400 as a co-surfactant, and Tween 80 as a surfactant. The resulting nanoemulsion displayed an average droplet size of 24.9 nm, a polydispersity index (PDI) of 0.748 ± 0.04, and a zeta potential of -0.1 mV, indicating nanoscale size and colloidal stability. In vitro release studies showed a controlled release pattern of the drug over time. These findings suggest that intranasal administration of DPZ-NE could be a promising approach in Alzheimer's treatment, following Higuchi kinetics, suggesting a diffusion-controlled mechanism. In vivo neuroprotective activity was assessed using a scopolamine-induced dementia model in Wistar rats. Behavioral tests, including the Morris water maze and active avoidance response, demonstrated significant cognitive improvements in DPZ-NE-treated animals compared to the control. Biochemical assays showed reduced acetylcholinesterase activity and enhanced antioxidant enzyme levels, indicating neuroprotection. Histopathological analysis confirmed reduced amyloid plaque formation and neuronal degeneration. These findings suggest that intranasal DPZ-NE effectively enhances drug bioavailability, facilitates BBB penetration, making it a promising approach for Alzheimer’s treatment. Further studies are required to assess its clinical potential. https://biomedpharmajournal.org/vol19no2/development-of-a-brain-targeted-donepezil-nanoemulsion-via-intranasal-route-with-pharmacodynamic-study-for-alzheimers-management/ : Alzheimer’s Disease Blood-Brain Barrier Donepezil Intranasal Delivery Neuroprotection Nanoemulsion