Capsule-based ultrasound-mediated targeted gastrointestinal drug delivery

Diseases which are prevalent in the gastrointestinal (GI) tract, such as Crohn's disease, are a topic of increasing concern because diagnosis and specific treatment are difficult and may be ineffective. New techniques are therefore sought after and this paper describes a proof-of-concept tethered capsule for targeted drug delivery (TDD) in the GI tract. The capsule consists of a camera, illumination, a drug delivery channel and an ultrasound (US) transducer. The transducer is described in detail, including a comparison of different piezoceramic materials that has been carried out. It was found that PZ54 (Ferroperm Piezoceramics, Kvistgaard, Denmark) was the most suitable material for our application. When driven at 4 Vpp, the outer diameter 5 mm PZ54 transducer operates at a frequency f = 4.05 MHz providing an acoustic pressure, Pac = 125 kPa, with a beam diameter, BD = 0.75 mm at the focus. Pressures in the range 50 - 300 kPa have been previously reported as suitable for sonoporation, a process vital in many TDD applications, so this is a promising result. Basic functional testing of the capsule was performed by supplying glass microbubbles (MBs) through the drug delivery channel into the US focus, monitored via the onboard camera. It was found that the acoustic radiation forces have a clear influence on the MBs, significantly changing their direction at the US focus. This suggests that drugs may be targeted to specific tissue in the GI tract by the new capsule. The results translate into a capsule configuration with the potential to be clinically and biologically useful.