Migraine is a debilitating neurological disorder that demands fast and effective therapeutic intervention. Traditional oral and parenteral routes are often limited by gastrointestinal disturbances, hepatic first-pass metabolism, delayed onset of action, and poor patient compliance, especially during acute attacks. Nose-to-brain drug delivery presents a promising, non-invasive alternative that bypasses the blood-brain barrier (BBB) via the olfactory and trigeminal nerve pathways, enabling direct drug transport to the central nervous system (CNS).
This review comprehensively explores recent technological and formulation advancements in intranasal drug delivery systems for migraine therapy. Emphasis is placed on novel carriers such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, micelles, and nanoemulsions, which enhance drug solubility, retention, and CNS targeting. Advanced delivery devices such as Precision Olfactory Delivery (POD®) systems and breath-powered nasal applicators have demonstrated improved deposition into the upper nasal cavity, enhancing therapeutic outcomes.
Preclinical and clinical studies, including FDA-approved formulations like Zomig, ONZETRA Xsail, and Zavzpret (zavegepant), are discussed to highlight their efficacy, safety, and patient-centric benefits. Additionally, the integration of mucoadhesive and in-situ gelling systems, thermosensitive polymers, and combination therapies has further improved nasal drug retention and bioavailability.
Future directions include personalized nasal delivery platforms, smart responsive materials, and AI-integrated biosensor-enabled systems for real-time monitoring and targeted administration. Collectively, these advancements underscore the growing potential of nose-to-brain strategies to revolutionize migraine treatment by providing rapid, targeted, and patient-friendly therapeutic solutions.