Developing intranasally administered electro-responsive nanodrugs for rapid epilepsy treatment

Epilepsy is a prevalent neurological disorder, with antiepileptic drugs serving as the cornerstone of clinical treatment. However, oral antiepileptic drugs are limited by issues such as low absorption rates, poor bioavailability, and significant toxic side effects. Although nanodrug delivery systems have shown considerable promise in improving drug efficacy and minimizing side effects, they are hindered by biological barriers, particularly the blood-brain barrier (BBB). Intranasal administration of nanodrugs presents a distinct advantage, as it can bypass the BBB and deliver drugs directly to the brain with rapid absorption, making it especially suitable for the treatment of acute epilepsy and status epilepticus. In response to this need, we have designed and synthesized an electrically responsive nanodrug for intranasal delivery that releases the antiepileptic drug in response to abnormal electrical activity during seizures. By capitalizing on the fast brain-targeting capability of intranasal administration, these nanoparticles quickly penetrate the brain and react to the irregular electrical currents generated by seizures, facilitating rapid drug release. This innovative approach provides a timely and effective means of alleviating acute epilepsy and status epilepticus, offering a rapid, targeted strategy for delivering antiepileptic drugs. • Nanodrugs bypass the blood-brain barrier through intranasal administration, enabling direct and rapid brain delivery. • Electrically responsive nanodrugs release antiepileptic drugs during seizures, enhancing treatment efficacy. • Targeted approach provides a timely, effective strategy for managing epilepsy, offering rapid site-specific drug release.