Electro-responsive drug delivery system for epilepsy therapy / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Temporal lobe epilepsy is a common neurological disease caused by abnormal syn-chronized 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 transmis-sion of epileptic discharges.METHODS The DDS was fab-ricated 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 physio-chemical properties of the nanomaterials.In vitro study based on a home-made electric device and high perfor-mance liquid chromatography was performed to record drug release profiles.Three epileptic models including acute,continuous and spontaneous models were estab-lished 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 electro-responsive drug release and brain-targeted accumula-tion.The DDS could increase the AEDs accumulation at epileptic region and release the AEDs in response to the epileptic discharges.Such strategy could timely inhib-it 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.