Magnetic targeting of microbubbles at physiologically relevant flow rates.
Owen JW., Rademeyer P., Stride E.
The localization of microbubbles to a target site has been shown to be essential to their effectiveness in ultrasound mediated drug delivery and gene therapy. The incorporation of super paramagnetic nanoparticles into the microbubble coating enables them to be manipulated using an externally applied magnetic field. Magnetic microbubbles have been shown to be effective in therapeutic delivery both in vitro and in vivo in a mouse model. The aim of this experiment was to determine under what conditions in the human body magnetic microbubbles can be successfully imaged and targeted. Different flow rates and shear rates were generated in a tissue mimicking phantom and targeting was observed using a 9.4 MHz ultrasound imaging probe. For the highest shear rates, targeting was also observed optically. Results indicate that magnetic microbubbles can be successfully targeted at shear rates found in the human capillary system (>1000/s) and at flow rates found in the veins and smaller arteries (~200 ml/s). Successful retention was also demonstrated in a perfused porcine liver model simulating conditions in vivo. This study provides further evidence for the potential of magnetic microbubbles for targeted therapeutic delivery.