Nose‐to‐brain delivery of nanotherapeutics: Transport mechanisms and applications

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.