Dual targeting nanoparticles for epilepsy therapy

Abstract

For epilepsy therapy, one-third of the patients worldwide are resistant to antiepileptic drugs mainly due to the existence of the blood–brain barrier (BBB) that prevents the drugs from reaching the epileptic lesions. Here, we design a double targeting nanoparticle carrying lamotrigine (LTG) to cross the BBB and further concentrate at the neurons. We prepare the nanoparticles on a microfluidic chip by encapsulating LTG in poly(lactic-co-glycolic acid) (PLGA) to form a core (PL) and capping the core with a shell of lipids conjugated with the D-T7 peptide (targeting the BBB) and Tet1 peptide (targeting the neuron) to form D-T7/Tet1-lipids@PL nanoparticles (NPs). In vitro and in vivo experiments show that D-T7/Tet1-lipids@PL NPs have excellent neuron targeting, antiepileptic, and protecting effects. Our approach provides a new strategy for improving the therapeutic efficacy of existing antiepileptic drugs.