Electric and reactive oxygen species dual-responsive polymeric micelles improve the therapeutic efficacy of lamotrigine in pentylenetetrazole kindling rats

Abstract

Although nanocarriers hold great promise for treating epilepsy by improving target drug delivery, on-demand drug release remains a significant challenge. We previously developed electro-responsive brain-targeting Pluronic F127/ferrocene (Fc) modified D-α-tocopherol polyethylene glycol succinate mixed micelles (FTC) micelles to optimize the delivery of antiseizure drug lamotrigine (LTG). However, the responsive characteristics are still not fully understood and the therapeutic effect of this responsive drug delivery system in epilepsy model is yet to be confirmed. Except for electricity, we discovered that such Fc functionalized mixed micelles delivered LTG in a triggered manner precisely controlled by H2O2. Furthermore, a study on pentylenetetrazole kindling rats revealed that the as-prepared LTG-loaded FTC micelles not only improved the antiseizure effects of LTG, but also exerted antiepileptogenesis function at a much lower dose than the free formulation. Hippocampal neuron loss was also reversed after treatment with responsive micelles. Our findings show that FTC micelles are responsive to both electric and reactive oxygen species, suggesting their use as a novel vehicle for on-demand treatment of epilepsy.