1. A versatile method for the preparation of particle-loaded microbubbles for multimodality imaging and targeted drug delivery
- Author
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Dario Carugo, Joshua Owen, Estelle Beguin, Eleanor Stride, Calum Crake, Alexandre A. Khrapitchev, Nicola R. Sibson, Richard Browning, and Jeong Yu Lee
- Subjects
Materials science ,Magnetic ,Drug Compounding ,Contrast Media ,Pharmaceutical Science ,Nanoparticle ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Contrast agents ,Drug Delivery Systems ,Microscopy, Electron, Transmission ,Cell Line, Tumor ,Ultrasound ,Methods Article ,Humans ,Particle Size ,RNA, Small Interfering ,Magnetite Nanoparticles ,Phospholipids ,Fluorescent Dyes ,Ultrasonography ,Targeting ,Microbubbles ,business.industry ,fungi ,Echogenicity ,food and beverages ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,0104 chemical sciences ,Microscopy, Fluorescence ,Targeted drug delivery ,Drug delivery ,Particle ,Magnetic nanoparticles ,0210 nano-technology ,business - 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. Electronic supplementary material The online version of this article (doi:10.1007/s13346-017-0366-7) contains supplementary material, which is available to authorized users.
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