Prototypical madness: Design and demonstration of a magnetic-acoustic targeted drug delivery system

Abstract

Ultrasound, microbubbles, and magnetic nanoparticles have been used both separately and in varying combinations for targeted drug delivery. Recent studies have demonstrated the therapeutic benefit of magnetic microbubble (MMB) retention and acoustic targeting using separate devices. As a developmental step towards clinical implementation, a magnetic-acoustic device (MAD) was designed for the purpose of generating co-aligned magnetic and acoustic fields with a single hand-held enclosure. This paper presents in vitro characterization and in vivo demonstration of a targeted therapeutic system wherein the MAD non-invasively retains and activates drug-loaded MMBs. Free field experiments were conducted in order to characterize the magnetic field and its gradient for MMB capture, and to quantify acoustic field strength and directivity. Flow phantom experiments were used to quantify MMB retention and illustrate the resulting enhancement of cavitation activity. Murine experiments then demonstrated therapeutic efficacy in a pancreatic cancer model, showing a significant benefit in comparison to the use of separate magnetic and ultrasonic devices.