Nose-to-Brain Nanocarriers for Migraine Management: A Comprehensive Review of Drug Delivery Strategies and Translational Challenges.

Migraine is among the most prevalent neurological disorders and can affect people's daily activities because of high- and long-lasting pain intensity attacks. The available dosage forms, such as oral and parenteral formulations, can enhance patients' symptoms but still have poor side effects, bioavailability, or dosing difficulty. As a result, there is an urgent need to find other novel drug delivery systems (DDSs) to treat migraine. The intranasal (IN) route was investigated as an alternative pathway to deliver therapeutic molecules directly to the brain, bypassing the blood-brain barrier (BBB) and hepatic first-pass metabolism. Nanocarriers facilitate drug transportation regardless of their lipophilicity, resulting in more efficient drug absorption and bioavailability. They also effectively contribute to brain targeting, which maximizes the therapeutic effect of drugs. This review discusses the efficacy of nanocarriers loaded with antimigraine agents and delivered by the IN route in the management of migraine. In preclinical studies, nanocarriers such as liposomes, ethosomes, nanostructured lipid carriers, and many others have been used to enhance brain targeting. Studies have focused on obtaining high results for brain pharmacokinetics, such as drug targeting efficiency (DTE) and direct transport percentage (DTP). This leads to better drug accumulation and a rapid onset of action. Despite the proven success of preclinical studies on the delivery of migraine drugs loaded with nanocarriers through the IN route, there is still a shortage in translating this success into the clinical stage.