Galantamine Nanoparticles Outperform Oral Galantamine in An Alzheimer’S Rat Model: Pharmacokinetics and Pharmacodynamics

Abstract

<b>Aim:</b> Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. <b>Materials & methods:</b> Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. <b>Results:</b> G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. <b>Conclusion:</b> G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.