Nanocarrier-based intranasal drug delivery: A transformative strategy for brain-targeted epilepsy therapy

Epilepsy, a chronic neurological disorder marked by recurrent seizures, remains a major global health concern due to limitations in current therapeutic strategies. Conventional antiepileptic drugs (AEDs) such as phenytoin, valproate, lamotrigine, and levetiracetam often exhibit poor solubility, low bioavailability, extensive hepatic metabolism, and restricted permeability across the blood–brain barrier (BBB). These pharmacokinetic and physiological barriers contribute to delayed onset of action, systemic toxicity, and subtherapeutic brain concentrations—particularly problematic in status epilepticus and drug-resistant epilepsy (DRE), which affects nearly 30–40% of patients. Nanotechnology-based delivery platforms have emerged as transformative approaches to overcome these limitations. Systems such as nanoemulsions, microemulsions, nanostructured lipid carriers (NLCs), polymeric micelles, PLGA nanoparticles (PLGA-NPs), and chitosan-based nanoparticles offer enhanced solubility, controlled release, and improved BBB penetration. Among these, intranasal drug delivery—especially via nasal sprays—has gained prominence for its ability to bypass the BBB through olfactory and trigeminal pathways, enabling rapid and targeted brain delivery while minimizing systemic side effects. These nanocarrier-based intranasal systems demonstrate superior pharmacokinetic performance, improved bioavailability, and reduced dosing frequency, offering a patient-friendly alternative for epilepsy management. This review comprehensively discusses recent advancements in nanoparticle-mediated intranasal drug delivery for epilepsy, highlighting formulation strategies, mechanisms of brain targeting, and translational potential. Overall, the integration of nanocarrier-based intranasal delivery systems into clinical practice holds significant promise for improving therapeutic efficacy, patient compliance, and personalized management of refractory epilepsy in future clinical settings.