Bridging the Gap: Harnessing Phytochemical-Loaded Nanocarriers for Enhanced Epilepsy Treatment

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, posing a significant global public health burden. While conventional anti-seizure medications remain the primary therapeutic option, their limited efficacy, systemic adverse effects, and inadequate penetration across the blood-brain barrier (BBB) have driven interest in alternative strategies. Phytochemicals derived from medicinal plants such as resveratrol, chrysin, berberine, crocin, and quercetin have demonstrated notable neuroprotective and anticonvulsant effects through mechanisms including modulation of neurotransmission, antioxidant activity, and anti-inflammatory action. However, their clinical application is hindered by poor aqueous solubility, low bioavailability, and instability, which limit their pharmacokinetic performance and therapeutic effectiveness. To overcome these limitations, nanocarrier-based drug delivery systems have emerged as promising platforms for enhancing central nervous system targeting and therapeutic efficacy. Preclinical evidence from rodent models of epilepsy indicates that phytochemical-loaded nanocarriers such as nanoemulsions, liposomes, polymeric nanoparticles, and solid lipid nanoparticles can improve drug stability, facilitate BBB crossing, attenuate neuroinflammation, and reduce seizure frequency and severity with minimal systemic toxicity. This review consolidates current findings on phytochemical-loaded nanocarriers for managing epileptic seizures, focusing on delivery mechanisms, molecular targets, pharmacological performance, and comparative efficacy relative to conventional forms. Despite ongoing challenges related to compound stability, nanoparticle biocompatibility, and industrial scalability, the integration of phytotherapy with nanotechnology represents a promising multifaceted approach for epilepsy treatment. Continued translational and clinical investigations will be crucial to validate these strategies and establish their role in future therapeutic protocols.