Nanoparticle-Mediated Nose-to-Brain Drug Delivery Systems: A Promising Approach for CNS Therapeutics

Abstract

The nose-to-brain delivery of drugs by nanoparticles has developed as an attractive non-invasive drug delivery methodology in order to circumvent the constraints of traditional central nervous system (CNS) therapeutics, especially the constraining quality of the blood-brain barrier (BBB). Nasal delivery allows direct delivery of the drugs to the brain through the olfactory-trigeminal neural pathway and improves drug bioavailability and decreases systemic exposure. Combining the intranasal delivery systems with nanotechnology has several benefits, such as increased solubility of drugs, resistance to enzyme degradation, controlled drug release, and delivery to the selected parts of the brain. Nanoparticulate carriers including polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, and nanoemulsions have been widely studied towards this effect. These systems allow an increase in the permeation of the nasal mucosa and increase the residence time, leading to an increase in the efficacy of the therapy in the treatment of neurological disorders like Alzheimer disease, Parkinson disease, epilepsy, and brain tumors. Although encouraging results have been seen in preclinical studies, various issues, such as mucociliary clearance, formulation stability, scalability, and regulatory factors are still a challenge. Recent developments on the surface modification and ligand-mediated targeting have further improved brain uptake and specificity. This review brings out the mechanisms, types of nanoparticles, formulation strategies, and recent advances in the nanoparticle-mediated nose-to-brain drug delivery systems and their potential in enhancing CNS therapeutics. In general, it is a revolutionize platform that has a great potential in future clinical application.