Magnetic targeting of microbubbles against physiologically relevant flow conditions

Abstract

The localization of microbubbles to a treatment site has been shown to be essential to their effectiveness in therapeutic applications such as targeted drug delivery and gene therapy. A variety of different strategies for achieving localization has been investigated, including biochemical targeting, acoustic radiation force, and the incorporation of superparamagnetic nanoparticles into microbubbles to enable their manipulation using an externally applied magnetic field. The third of these strategies has the advantage of concentrating microbubbles in a target region without exposing them to ultrasound, and can be used in conjunction with biochemical targeting to achieve greater specificity. Magnetic microbubbles have been shown to be effective for therapeutic delivery in vitro and in vivo. Whether this technique can be successfully applied in humans however remains an open question. The aim of this study was to determine the range of flow conditions under which targeting could be achieved. In vitro results indicate that magnetic microbubbles can be retained using clinically acceptable magnetic fields, for both the high shear rates (approx. 104 s−1) found in human arterioles and capillaries, and the high flow rates (approx. 3.5 ml s−1) of human arteries. The potential for human in vivo microbubble retention was further demonstrated using a perfused porcine liver model.

Sonothrombolysis with Magnetically Targeted Microbubbles

“…depths up to a few tens of millimeters in the body depending on the flow rate (Barnsley et al 2015(Barnsley et al , 2016Owen et al 2015). This is sufficient for treating clots in the middle cerebral artery (Gillard et al 1986), one of the brain vessels most commonly affected by ischaemic stroke (Demchuk et al 2001).…”

A Combined Magnetic‐Acoustic Device for Simultaneous, Coaligned Application of Magnetic and Ultrasonic Fields

“…Microbubbles have been used clinically for decades as ultrasound contrast agents . In recent work they have been investigated as drug delivery carriers and for magnetic drug targeting . An integrated drug delivery device for simultaneously localizing and activating carriers that rely on acoustic and magnetic modalities would be highly advantageous for these types of applications.…”

Introduction for amazing (cavitation) bubbles

“…The presentation paper by Stride and co-workers [11] found the magnetic approach is superior over other localization approaches for in vivo microbubble retention, which was further demonstrated using a perfused porcine liver model.…”