Electro-responsive micelle-based universal drug delivery system for on-demand therapy in epilepsy

A universal drug delivery system (DDS) with brain-targeted ability is demanded to enhance antiepileptic therapeutic efficacy and reduce side effects in multiple types of epileptic seizures. In this study, we reported a micelle-based DDS possessing the brain-targeted ability and electro-responsive feature for universal delivery of antiepileptic drugs (AEDs). The system is fabricated by ferrocene (Fc)-conjugated D-a-tocopherol polyethylene glycol succinate and amphiphilic block copolymer, which improve the drug encapsulation of different AEDs. Interestingly, the intrinsic nature of TPGS-Fc including transferrin receptor-mediated transcytosis and efflux pump inhibition endows the system with high permeability across the blood-brain barrier. Based on the hydrophobic-hydrophilic transition of Fc, the micelles can respond to epileptiform discharges and thus release the loaded AEDs. Improved antiepileptic efficacy of the micelles has been demonstrated in acute, continuous, and chronic epilepsy models. In summary, we have developed a universal micelle-based DDS for various AEDs delivery, which provides a promising approach to on-demand therapy of different epileptic seizures.