Epileptogenic zone-targeting nanoparticle drug delivery system for antiseizure medication.

Epilepsy is a chronic neurological disorder affecting over 65 million people worldwide, characterized by abnormal excessive excitation of neuronal networks. Traditional antiseizure medications (ASMs), such as phenytoin (PHT), have limited therapeutic efficacy due to poor blood-brain barrier (BBB) penetration and off-target toxicity. To address these issues, this study proposes an electrically responsive closed-loop system drug delivery system (DDS) using PHT as a model drug. The system utilizes electro-responsive nanoparticles made from polypyrrole (PPY), which can contract in response to electrical stimulation, allowing for on-demand drug release during epileptic discharges. Additionally, the excessive activation of tryptophan metabolism in people with epilepsy leads to tryptophan (Trp) depletion, promoting its uptake in the epileptogenic zone and creating a "metabolic trapping" effect. Meanwhile, hyaluronic acid (HA) binds to CD44 receptors, enhancing nanoparticle retention at the lesion, thereby creating a "targeted delivery-extended retention" effect. This non-invasive epileptogenic zone-targeting PPY-HA-PHT-Trp DDS may enhance ASM effect and have potential applications in clinical settings.