Development And In Vivo Evaluation Of An Intranasal Nano Emulsion-Based Nose-To-Brain Delivery System For Enhanced Therapeutic Efficacy In Alzheimer’s Disease

Abstract

Nanoemulsions, which are nanostructured and colloidally stabilized materials, have emerged as a promising approach for drug delivery. A major challenge in treating Alzheimer's disease (AD) is overcoming the blood-brain barrier (BBB) to deliver therapeutic agents effectively to the brain. The goal of this study was to develop a Rivastigmine (RSG) loaded nanoemulsion that can enhance the treatment for AD patients. We formulated a nanoemulsion containing RSG by incorporating pyridoxine, an essential vitamin for central nervous system function, along with linseed oil, which acted as the lipophilic phase in the formulation. Nine different formulations were created using the emulsification method and were then characterized. The formulation labeled “RF6” exhibited the highest drug entrapment efficiency, with 83.25% of the drug retained, likely due to its higher linseed oil content. In-vitro drug release studies conducted using a Franz diffusion cell showed that the "RF6" formulation provided a sustained release of the drug. The optimal formulation, with a globular size of 203.4 nm, was further analyzed using various techniques, including zeta potential analysis, ATR, DSC, and XRD. Cognitive performance in Long-Evans rats with AD was evaluated using the Morris Water Maze (MWM) model. The findings of this study suggest that the combination of RSG nanoemulsion with linseed oil and pyridoxine reduced the travel distance in the animal model, offering potential therapeutic benefits for AD patients.