Electro-responsive drug delivery system for epilepsy therapy

OBJECTIVE Temporal lobe epilepsy is a common neurological disease caused by abnormal synchronized discharge in the brain and it is mainly treated through long-term use of anti-epileptic drugs(AEDs). This project is supposed to provide an electro-responsive and brain-targeted drug delivery system(DDS) for on-demand drug release, which could promptly block the transmission of epileptic discharges. METHODS The DDS was fabricated by co-polymerization of dopamine and pyrrole,together with conjugation of brain-targeted peptide. A number of characterization including electron microscopy,thermogravimetric analysis, dynamic light scattering and other methods were conducted to evaluate the physiochemical properties of the nanomaterials. In vitro study based on a home-made electric device and high performance liquid chromatography was performed to record drug release profiles. Three epileptic models including acute, continuous and spontaneous models were established for the evaluation of therapeutic efficacy. RESULTS Our polymeric DDS has a nanoscale size(ca. 80 nm)and could load AEDs such as phenytoin(drug loading capacity 20.4%). The hybrid nanomaterials can improve the brain delivery efficiency through a combination of receptor-mediated transcytosis and near-infrared-enabled brain transport. In vitro study proved that the DDS could release phenytoin in the electric field in a sensitive(50 μA), quick(30 s) and sustained(> 3 times) manner.In vivo study demonstrated excellent anti-epileptic effects in a lower dose(20%). Biosafety study further verified that our strategy has limited damage. CONCLUSION For on-demand seizure control, we have developed a nano-engineered DDS with the capability of electroresponsive drug release and brain-targeted accumulation. The DDS could increase the AEDs accumulation at epileptic region and release the AEDs in response to the epileptic discharges. Such strategy could timely inhibit the epileptic seizure. Our work provides a promising approach to "smart" therapy of epilepsy and sheds light on development of pharmacotherapy of other brain disorders.