Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy

Long-term pharmacotherapy, serving as the main therapeutic approach for epilepsy prophylaxis, has suffered from limited efficacy and potential side effects because of the blood-brain barrier (BBB) and untimely medication. Here, we reported a nanoengineered drug delivery system for synergistic brain-targeting delivery and on-demand drug release of antiepileptic drugs (AEDs). The dopamine-pyrrole hybrid system can improve delivery efficiency through a combination of receptor-mediated transcytosis and BBB disruption-enabled transport induced by photothermal conversion of near-infrared light. Incorporation of polydopamine endowed the delivery system with enhanced conductivity and sensitivity, giving sustained (2 hours) and rapid (30 s) drug release in response to epileptiform discharges. Acute, continuous, and spontaneous seizure models validated that the delivery system could inhibit seizures upon epileptiform abnormalities, treated by one-fifth of the conventional dosage. Complemented with satisfactory biosafety results, this smart modality is promising to be an effective and safe strategy to improve the therapeutic index of AEDs for epilepsy.

Automated summary

This study reports a nanoengineered drug delivery system for improved delivery efficiency and on-demand drug release of antiepileptic drugs (AEDs). The system utilizes receptor-mediated transcytosis and blood-brain barrier disruption induced by photothermal conversion to achieve brain-targeted delivery. The system has been shown to effectively inhibit seizures upon epileptiform abnormalities, using only one-fifth of the conventional dosage, and holds promise for clinical applications.