EVALUATING THE THERAPEUTIC EFFICACY OF METFORMIN-BERBERINE LOADED NANOPARTICLES FOR THE TREATMENT OF TYPE 2 DIABETES-INDUCED ALZHEIMER’S DISEASE

Objective: To develop and evaluate a novel drug delivery system (NDDS) of Metformin and Berberine-loaded solid lipid nanoparticles (MBSLNPs) for neuroprotection in type 2 diabetes mellitus (T2DM) induced Alzheimer’s disease (AD) model. Methods: MBSLNPs were prepared by hot homogenization and ultrasonication, characterized for particle size, zeta potential, drug loading, and FTIR (fourier transform infrared spectroscopy) compatibility. In vitro release kinetics were modeled, and in vivo efficacy was assessed in a combined streptozotocin (STZ) and amyloid-β (Aβ) rat model by performing behavioral, biochemical, and histopathological analyses. Safety of blank SLNs was evaluated in healthy rats. Results: MBSLNPs exhibited a mean particle size of 102±5 nm, zeta potential of –29±3mV, and high drug loading, with no FTIR incompatibilities. Drug release followed first-order kinetics (R²=0.9955) with Fickian diffusion (n=0.43). In vivo, MBSLNPs significantly improved memory performance in Morris Water Maze and Y-Maze compared with free drug (p