Alzheimer's disease (AD) is a form of dementia characterized by neuronal damage and the buildup of abnormal proteins such as beta-amyloid and phosphorylated tau. PLGA (Poly (lactic-co-glycolic acid)) nanoparticles are extensively employed drug delivery platforms, known for their biocompatibility, biodegradability, sustained drug release, and targeted delivery capabilities. Leveraging the potentials of PLGA nanoparticle formulations in targeted drug delivery can significantly impact AD disease management and progression control. In this study, memantine (MEM) loaded PLGA nanoparticle formulations were developed and optimized using the double emulsion technique, to be used for treatment of AD. A novel LC-MS/MS method was developed by our group and was used to analyze the prepared MEM-loaded formulations. The MEM-loaded PLGA nanoparticles were characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and in-vitro release. Optimization parameters for particle size, including MEM concentration, PLGA concentration, surfactant concentration, and sonication time were tested. The in-vitro drug release studies were investigated using two different formulations containing D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) and polyvinyl alcohol (PVA) as surfactants. A higher encapsulation efficiency (EE) (55 ± 5.6 %) as well as higher drug release (25 %) was found in TPGS-containing formulation, highlighting the crucial role of the nature of surfactant in the MEM-loaded PLGA nanoparticle system. The concentration of the surfactant, polymer and the drug molecule were also found to influence the efficiency of the formulation. The morphological analysis of nanoparticles across all formulations revealed their spherical shape. Cytotoxicity evaluation was conducted using the MTT assay with the SH-SY5Y cell line, indicating maximum cytotoxicity of 74.94 ± 7.7 % following a 48-h incubation period. In vitro characterization studies demonstrated that MEM-loaded PLGA formulations could provide targeted and sustained drug delivery for Alzheimer's disease treatment without inducing cytotoxic effects.