title: 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. 10(4) 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.
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Owen
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Rademeyer
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK ; Nuffield Department of Surgical Sciences , University of Oxford , John Radcliffe Hospital, Oxford OX3 9DU , UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chung
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK ; Nuffield Department of Surgical Sciences , University of Oxford , John Radcliffe Hospital, Oxford OX3 9DU , UK.
authors.forename: David
authors.initials: D
authors.lastname: Holroyd
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK.
authors.forename: Constantin
authors.initials: C
authors.lastname: Coussios
authors.affiliation: Nuffield Department of Surgical Sciences , University of Oxford , John Radcliffe Hospital, Oxford OX3 9DU , UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Friend
authors.affiliation: Healthcare Biomagnetics Laboratory , University College London , 21 Albemarle Street, London W1S 4BS , UK ; Institute of Biomedical Engineering , University College London , Gower Street, London WC1E 6BT , UK.
authors.forename: Quentin A
authors.initials: QA
authors.lastname: Pankhurst
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science , University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ , UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Stride
keywords: contrast agent; drug delivery; imaging; magnetic targeting; microbubbles; ultrasound