Nanocarriers-mediated nose-to-brain drug delivery: A novel approach for the management of Alzheimer’s disease

Alzheimer's disease is a neurodegenerative disorder affecting wide range of the population worldwide and 6th primary cause of death in the USA. The available conventional treatment strategies for Alzheimer's disease remain insufficient due to the existence of blood-brain barrier, first pass metabolism, peripheral side effects, which limits the drug concentration at the targeted site. In this perspective, the nose-to-brain delivery of therapeutic agents has emerged as an alternative strategy over the conventional (oral and parenteral) delivery systems. Nose-to-brain strategy utilizes the unique architectural and physiological characteristic of nasal cavity, and it delivers the drug directly to the brain via olfactory route, which enhance accumulation of drug in the brain. However, there are several drawbacks associated with the intranasal drug delivery including mucociliary clearance, poor permeation and 'nasal first pass effect'. Therefore, several approaches were explored to overcome the challenges associated with the nose-to-brain delivery route such as utilization of mucoadhesive agents or permeation enhancer or both, and delivery of bioactives via nanocarrier systems. In this review, we have explored the nose-to-brain administration route for the therapeutic interventions of Alzheimer's disease. Through this review, we have tried to capture the attention of scientists working for the treatment strategies of Alzheimer's disease, where the compilation of nanocarriers including polymeric nanocarriers, lipid-based nanoparticles, nanoemulsion and microemulsions that could be an effective approach towards the practical applicability of nose-to-brain delivery has been made.