Intranasal Biodegradable Nanomedicine for Epilepsy Management: Targeting the Brain Beyond the Blood-Brain Barrier

Epilepsy is a common chronic neurological disorder characterized by recurrent, unprovoked seizures arising from abnormal neuronal hyperexcitability and hypersynchronous electrical activity within the brain. Despite advances in antiseizure medications, effective epilepsy management remains challenging because of pharmacoresistance, limited blood-brain barrier (BBB) permeability, inadequate intracerebral drug accumulation, and systemic toxicity. Moreover, currently available therapies primarily provide symptomatic seizure control without addressing the fundamental pathological processes involved in epileptogenesis, neuroinflammation, oxidative stress, and neuronal degeneration. Intranasal administration has emerged as an attractive non-invasive approach for direct brain targeting, enabling therapeutic agents to circumvent BBB-associated transport barriers and access the central nervous system through the olfactory and trigeminal neural pathways. In this context, biodegradable nanomedicine platforms have gained considerable attention due to their favorable biocompatibility, controlled drug release, enhanced mucosal permeation, and potential for targeted intracerebral delivery. This review provides a comprehensive and critical overview of recent advances in intranasal biodegradable nanomedicine for epilepsy, integrating current knowledge on disease pathophysiology, biological and pharmaceutical barriers, nose-to-brain transport mechanisms, biodegradable nanoparticle platforms, and emerging functionalization strategies. Importantly, the review critically evaluates the current evidence, distinguishing encouraging preclinical findings and discusses the major translational challenges that continue to hinder clinical implementation. Finally, future perspectives are highlighted to identify opportunities for developing safer, more effective, and clinically translatable therapies for epilepsy management.