Ultrasound Microbubble Contrast Agents Promote Transdermal Drug Delivery

Abstract

This report discusses a new development in the use of ultrasound (US) microbubble contrast agents on transdermal drug delivery. In clinical applications, microbubbles serve as imaging agents to enhance the contrast of ultrasound images via intravenous injection. Different degrees of microbubble oscillation due to distinct acoustic fields can elicit various degrees of cavitation. Inertial cavitation can enhance the permeability in the surrounding tissues, increase vessel wall permeability, and promote drug entry from blood into cytosol or matrix, whereas stable cavitation can slightly increase tissue permeability without causing any harm. At present, most ultrasound contrast agents are designed for injection into blood vessels, nevertheless, microbubbles with different condition parameters are highly correlated with efficiency in transdermal permeation. As for applications in a transdermal drug delivery, we also used microbubbles at a given concentration in combination with ultrasound to widen intercellular spaces, thereby successfully enhancing the in vivo delivery of arbutin across the skin. In order for liquid-phase microbubbles to be conveniently applied to skin surface, our team modified the medium surrounding the microbubbles at the optimum concentration from liquid to gel. Moreover, it is found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface. Recently, US-mediated drug-coated microbubble cavitation for enhancing hair growth, the treatment of inflammatory skin diseases, and wound healing both in vitro and in vivo have been investigated by our group.