Nanocarrier-based intranasal drug delivery for enhanced neurological disorders treatment

The blood-brain barrier (BBB) represents a major obstacle in the treatment of neurological disorders. While it plays a crucial role in protecting the central nervous system (CNS) from harmful xenobiotics, it also limits the entry of drugs already in systemic circulation. Intranasal drug delivery has emerged as an interesting, non-invasive strategy to bypass the BBB by exploiting the anatomical connections provided by the olfactory and trigeminal nerves, allowing direct transport from the nasal cavity to the brain. Nevertheless, drugs administered via this route face several challenges, including enzymatic degradation, mucociliary clearance and limited residence time on the nasal mucosa. This review examines the underlying mechanisms of nose-to-brain drug transport and details how recent advances in nanocarrier-based delivery systems, including lipid-based, polymeric-based, protein-based, and inorganic nanoparticles, can be engineered to enhance drug delivery to the brain. Recent preclinical advances demonstrate improved brain targeting, protection from degradation, and controlled release profiles. Finally, we summarize the current clinical progress and provide our perspective on the steps needed for successful clinical translation, emphasizing the importance of optimizing nanosystem performance across both the nasal cavity and brain compartments.