Leveraging TRPV1 for intracellular delivery of membrane impermeant compounds in the brain

Large-pore ion channels present a window of opportunity for cell-specific intracellular drug delivery. Here, we demonstrate that the capsaicin receptor, TRPV1, can be used for delivery of the membrane impermeant lidocaine derivative QX-314 into neurons in the brain in vivo by using drug-induced hyperlocomotion as a behavioral readout and we validated our findings with ex vivo electrophysiological recordings. Our studies present evidence that this strategy can be used to deliver membrane impermeant compounds in the brain.