Ultrasound and microbubbles promote the retention of fluorescent compounds in the small intestine

Focused ultrasound (US) is a novel means to increase the passage of medication through the wall of the small intestine. The purpose of this study was to determine whether US and microbubbles (MBs) can facilitate delivery of macromolecular therapeutic agents across the intestinal epithelium in vitro and in vivo. In vitro experiments involved delivery of compounds across a cell monolayer, namely Caco-2 cells cultured on ThinCert filters. The cells were cultured for a minimum of 3 weeks to mimic the polarised intestinal epithelium. A suspension of dextran with or without MBs, prepared in growth medium, was introduced into the apical chamber of the ThinCert with a syringe pump through a channel in the centre of a miniature focused US transducer (4 MHz, 1 MPa PNP). Each in vivo experiment involved a tethered endoscopic capsule with an US transducer and a delivery channel inserted into the small intestine of a terminally anaesthetised pig via a surgical stoma. The amount of fluorescent dextran delivered across the Caco-2 monolayer when employing US, MBs and dextran was higher than the amount delivered with dextran alone. With this approach, fluorescent marking of the wall of the small intestine was achieved in vivo by applying US and MBs. Our work indicates that US has potential for application in targeted treatment of gastrointestinal disease and oral drug delivery.