LINALOOL AS ADJUNCTIVE ANTIEPILEPTIC THERAPY: A REVIEW ON NOSE TO BRAIN DRUG DELIVERY

Epilepsy is a multifactorial neurological disorder characterized by recurrent seizures resulting from aberrant neuronal discharge and impaired synaptic regulation within the central nervous system. Although currently available antiepileptic drugs provide symptomatic seizure suppression, their therapeutic utility is frequently compromised by pharmacoresistance, systemic toxicity, neurocognitive adverse effects, and restricted permeability across the blood–brain barrier. Consequently, the development of alternative brain-targeted therapeutic strategies has emerged as a significant area of neuropharmaceutical research. The present review systematically examines the therapeutic relevance of linalool, a naturally occurring bioactive monoterpene, as a potential adjunctive antiepileptic agent administered through the intranasal nose-to-brain pathway. Preclinical investigations have demonstrated that linalool exerts anticonvulsant and neuroprotective effects through modulation of GABAergic inhibitory signaling, attenuation of glutamatergic excitotoxicity, suppression of neuroinflammatory mediators, and reduction of oxidative neuronal damage. Intranasal administration facilitates rapid and direct transport of linalool to the brain via olfactory and trigeminal neural pathways, thereby circumventing the blood–brain barrier and hepatic first-pass metabolism. Furthermore, advanced nanoformulation-based delivery systems have shown enhanced nasal permeation, improved cerebral bioavailability, prolonged drug retention, and sustained therapeutic activity. Despite promising experimental outcomes, translational limitations persist due to inadequate clinical validation, variability in formulation strategies, insufficient pharmacokinetic characterization, and concerns regarding long-term safety and formulation stability. Collectively, the available scientific evidence supports the potential applicability of intranasal linalool delivery as an innovative adjunctive therapeutic approach for epilepsy management. Nevertheless, comprehensive clinical investigations and formulation standardization studies remain essential for establishing its therapeutic efficacy, safety profile, and future clinical applicability.