Theranostic USPIO‐Loaded Microbubbles for Mediating and Monitoring Blood‐Brain Barrier Permeation |
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| Authors: | Twan Lammers Patrick Koczera Stanley Fokong Felix Gremse Josef Ehling Michael Vogt Andrij Pich Gert Storm Marc van Zandvoort Fabian Kiessling |
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| Affiliation: | 1. Department for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany;2. Department of Controlled Drug Delivery, MIRA Institute for Biomedical Engineering and Technical Medicine, University of Twente, Enschede, The Netherlands;3. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;4. Institute for Molecular Cardiovascular, Research (IMCAR) University Clinic, RWTH Aachen University, Aachen, Germany;5. Functional and Interactive Polymers, DWI, Leibniz Centre for Interactive Materials, RWTH Aachen University, Aachen, Germany;6. Department of Genetics and Cell Biology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands |
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| Abstract: | Efficient and safe drug delivery across the blood‐brain barrier (BBB) remains one of the major challenges of biomedical and (nano‐) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)‐based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO‐MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non‐invasive R 2*‐based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)‐dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders. |
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| Keywords: | drug delivery hybrid materials magnetic nanoparticles medical applications stimuli‐responsive materials |
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