An In Vitro Sonication System for Applications in Ultrasound-mediated Targeted Drug Delivery

Ultrasound is a well-established imaging modality used in clinics worldwide for many different applications. It has also experienced recent growth in interest for therapeutic applications in the form of high-intensity focused ultrasound (HIFU) or focused ultrasound (focused-US), including in capsules for use in drug delivery in the gut. The work described here aimed to support the investigation of its usefulness for drug delivery further. An in vitro sonication system was designed, comprising a focused-US transducer, a cell plate on a vertical stage and transepithelial electrical resistance (TER) meter. Miniature focused-US transducers were fabricated with PZ26 and PZ54 materials (Meggitt Sensing Systems, Kvistgaard, Denmark). The active elements in both transducers have outer diameter, OD = 5 mm, and radius of curvature, R-C = 15 mm. US field mapping indicated that output acoustic pressures are in the range 25 kPa < P-ac < 210 kPa and acoustic powers in the range 8 mW < Power(ac) < 80 mW. Feasibility testing with Caco-2 colon cancer cells involved measuring TER during and after sonication. Sonication produced a drop in TER of 6.7% after 6 min. Recovery to the starting TER value was observed 14 min after sonication indicating that the sonication system can be used to measure the effect of ultrasound on tissue barrier function as expected.