Current Clinical Evidence on Nose-to-Brain Drug Delivery.

Intranasal delivery is increasingly recognised as a promising strategy for direct drug transport to the brain via the nose-to-brain pathway, bypassing the blood-brain barrier and improving therapeutic efficacy. This approach has shown potential in the treatment of neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and acute psychiatric conditions, as well as in emergencies such as anxiety attacks and migraine episodes. Recent clinical studies investigating intranasal formulations of rivastigmine, insulin, and olanzapine, among other drugs, have provided encouraging evidence supporting the clinical translation of this delivery strategy. In addition, FDA-approved intranasal products indicated for central nervous system disorders, including diazepam and midazolam for seizure management, and triptans for migraine, demonstrate the growing clinical relevance of intranasal drug delivery. Both preclinical and clinical studies have reported encouraging outcomes, particularly when intranasal delivery is combined with nanoformulations and specialised delivery devices designed to enhance olfactory deposition. Intranasal administration is non-invasive, painless, and may improve patient adherence while enhancing brain bioavailability. Nevertheless, further well-designed clinical studies are required to establish the long-term safety, efficacy, and clinical applicability of this delivery strategy.