Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

Apart from its clinical use in imaging, ultrasound has been thoroughly investigated as a tool to enhance drug delivery in a wide variety of applications. Therapeutic ultrasound, as such or combined with cavitating nuclei or microbubbles, has been explored to cross or permeabilize different biological barriers. This ability to access otherwise impermeable tissues in the body makes the combination of ultrasound and therapeutics very appealing to enhance drug delivery in situ. This review gives an overview of the most important biological barriers that can be tackled using ultrasound and aims to provide insight on how ultrasound has shown to improve accessibility as well as the biggest hurdles. In addition, we discuss the clinical applicability of therapeutic ultrasound with respect to the main challenges that must be addressed to enable the further progression of therapeutic ultrasound towards an effective, safe and easy-to-use treatment tailored for drug delivery in patients.