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Drug Deliv Transl Res. 2018 Apr;8(2):342-356. doi: 10.1007/s13346-017-0366-7.

A versatile method for the preparation of particle-loaded microbubbles for multimodality imaging and targeted drug delivery.

Author information

1
Institute of Biomedical Engineering, Department of Engineering Science, Old Road Campus Research Building, University of Oxford, Headington, Oxford, OX3 7DQ, UK.
2
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.
3
Faculty of Engineering and the Environment, University of Southampton, Southampton, UK.
4
Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, Old Road Campus Research Building, University of Oxford, Headington, Oxford, OX3 7DQ, UK.
5
Institute of Biomedical Engineering, Department of Engineering Science, Old Road Campus Research Building, University of Oxford, Headington, Oxford, OX3 7DQ, UK. eleanor.stride@eng.ox.ac.uk.

Abstract

Microbubbles are currently in clinical use as ultrasound contrast agents and under active investigation as mediators of ultrasound therapy. To improve the theranostic potential of microbubbles, nanoparticles can be attached to the bubble shell for imaging, targeting and/or enhancement of acoustic response. Existing methods for fabricating particle-loaded bubbles, however, require the use of polymers, oil layers or chemical reactions for particle incorporation; embed/attach the particles that can reduce echogenicity; impair biocompatibility; and/or involve multiple processing steps. Here, we describe a simple method to embed nanoparticles in a phospholipid-coated microbubble formulation that overcomes these limitations. Magnetic nanoparticles are used to demonstrate the method with a range of different microbubble formulations. The size distribution and yield of microbubbles are shown to be unaffected by the addition of the particles. We further show that the microbubbles can be retained against flow using a permanent magnet, can be visualised by both ultrasound and magnetic resonance imaging (MRI) and can be used to transfect SH-SY5Y cells with fluorescent small interfering RNA under the application of a magnetic field and ultrasound field.

KEYWORDS:

Contrast agents; Drug delivery; Magnetic; Microbubbles; Targeting; Ultrasound

PMID:
28299722
PMCID:
PMC5830459
DOI:
10.1007/s13346-017-0366-7
[Indexed for MEDLINE]
Free PMC Article

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