Ultrasound-Mediated Drug Delivery: From Bubble Physics to Cancer Therapy

Abstract

Beyond diagnostic imaging and contrast-enhanced ultrasound, microbubbles have shown immense promise in the field of drug delivery. In this work, we present several investigations of how ultrasound and microbubble physics may be exploited for imaging and therapy. We begin with an introduction on the challenges of drug delivery for cancer and how microbubble cavitation behavior may be exploited as a therapeutic strategy for overcoming these barriers (Chapter 1). We then describe how inertial cavitation, which is critical in many therapeutic applications of ultrasound, may be visualized in real-time with a clinical ultrasound scanner (Chapter 2). We then present evidence that unique microbubble nonlinear dynamics can produce a phase response that can be used to improve contrast imaging (Chapter 3). We then show a study of microbubble diffusion and destruction during therapeutic pulsing schemes in a common in vitro setup (Chapter 4). These above results present the building blocks to study ultrasound-mediated drug delivery in vivo using a clinical ultrasound scanner to evaluate efficacy in a murine model of hepatocellular carcinoma (Chapter 5) and safety in a healthy porcine model (Chapter 6). We conclude with a summary of the accomplishments and future directions of this work (Chapter 7).