Controlled Ultrasound Erosion for Transdermal Delivery and Hepatitis B Immunization

Although ultrasound is effective for transdermal delivery, it remains difficult to control the position, shape and size of localized skin transport regions. We developed an ultrasound erosion protocol to generate a single-site, circular delivery region with controlled size at the center of patched skin. We found that (i) shorter ultrasound pulses (25 cycles) with higher pulse repetition frequency (4 kHz) and higher peak negative pressure (17.0 MPa) resulted in larger (0.995 mm²) and deeper (∼300 µm) skin delivery regions with a higher success rate (94.44%); and (ii) temperature elevation of the skin increased with ultrasound exposure time, with a 30-s safety threshold. Furthermore, we found that hair follicles decreased the delivery controllability of ultrasound erosion. Therefore, we selected the skin of the hind legs of mice without dense hair follicles to deliver more than 1 μL of vaccine solution and successfully elicit immune responses against hepatitis B surface antigen.