Updated Progress of Nanocarrier-Based Intranasal Drug Delivery Systems for Treatment of Brain Diseases

Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson’s disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery. However, the multiple barriers in nose-to-brain route — including rapid mucociliary clearance in the nasal cavity, enzyme degradation, and the blood–brain barrier (BBB) — pose serious challenges to brain-targeted drug delivery. Hence, very limited translation from the laboratory to the clinic has been achieved. The present review highlights the surface modification of nanocarriers with different strategies devoted to facilitate nose-to-brain delivery: prolonging retention time in the nasal cavity, improving penetration ability, and promoting brain targeting with ligands. Additionally, in vitro blood–brain barrier models, influencing an efficient study on intranasal delivery of therapeutics into the brain through indirect nose-to-blood-to-brain pathway, is discussed.