Development of an Ingestible Fluid Wicking Gastric Electrical Stimulation Platform for Hormone Modulation

Abstract

Dysregulation of the gut-brain axis affects hundreds of millions of people annually, often resulting in motility, autoimmune, mood, and neurological disorders. Colloquially referred to as an “electroceutical,” electrical stimulation of the GI tract for modulation of this axis has been explored as a potential therapeutic for GI motility disorders. Thus far, these methods have utilized invasive implant procedures in order to stimulate the outer muscle layers of the stomach. The development of non-invasive stimulation approaches requires that these systems be in an ingestible form factor that instead stimulate the inner mucosal layer of the stomach. However, stimulation of the mucosal layer remains challenging due to gastric fluid that can disrupt targeted stimulation. In this work we first elucidate and establish the relationship between gastric electrical stimulation (GES) and the production of ghrelin, a hormone associated with hunger, in a pig model. Next, we translate this stimulation approach into a non-invasive capsule system that is then optimized through rapid iteration enabled by 3D printing and an in vitro system replicating the stomach’s mechanical and electrical properties. Finally, inspired by the fluid wicking skin of the Moloch horridus, we developed and integrated fluid wicking surface structures into the capsule that can displace fluid in order to mitigate the challenge it poses to targeted stimulation. The optimized capsule was administered in vivo in pigs and demonstrated the ability to modulate plasma ghrelin levels. The developments around the surface structure and properties to enable fluid displacement have broad ranging applications in low size, weight, and power (SWaP) ingestible mucoadhesive and fluid sampling systems.