Pulsed electrical stimulation enhances intestinal permeability

Abstract

Oral ingestion of drugs remains the most convenient method for pharmacotherapy. However, oral absorption is hampered by digestive enzymes and the intestinal epithelial barrier. Here we investigate the ability of electrical stimuli to biologically modulate intestinal permeability. We demonstrate that pulsed electrical stimulation increases intestinal permeability, facilitating transport of chemical species across the epithelium. We evaluate the effects of several stimulation parameters in silico and subsequently characterize the biological effects in vitro using Caco-2 colorectal cancer cells, and an acute in vivo intestinal model. Our findings suggest that these effects may be mediated through calcium-dependent interactions with tight junction proteins which induce a reversible permeability increase differing based on the total charge delivered, amplitude and frequency of the current delivered. Pulsed electrical stimulation could be a potential strategy for transiently modulating the intestinal barrier.