Characterizing Microbubble‐Mediated Permeabilization in a Vessel‐on‐a‐Chip Model
Small, vol. 21, pp. e2407550
Abstract
Abstract Drug transport from blood to extravascular tissue can locally be achieved by increasing the vascular permeability through ultrasound‐activated microbubbles. However, the mechanism remains unknown, including whether short and long cycles of ultrasound induce the same onset rate, spatial distribution, and amount of vascular permeability increase. Accurate models are necessary for insights into the mechanism so a microvessel‐on‐a‐chip is developed with a membrane‐free extravascular space. Using these microvessels‐on‐a‐chip, distinct differences between 2 MHz ultrasound treatments are shown with 10 or 1000 cycles. The onset rate is slower for 10 than 1000 cycles, while both cycle lengths increase the permeability in spot‐wise patterns without affecting microvessel viability. Significantly less vascular permeability increase and sonoporation are induced for 10 versus 1000 cycles at 750 kPa (i.e., the highest studied peak negative acoustic pressure (PNP)). The PNP threshold for vascular permeability increases is 750 versus 550 kPa for 10 versus 1000 cycles, while this is 750 versus 220 kPa for sonoporation. Vascular permeability increases do not correlate with α v β 3 ‐targeted microbubble behavior, while sonoporation correlates with α v β 3 ‐targeted microbubble clustering. In conclusion, the further mechanistic unraveling of vascular permeability increase by ultrasound‐activated microbubbles in a developed microvessel‐on‐a‐chip model aids the safe and efficient development of microbubble‐mediated drug transport.
Authors 11
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Erasmus MC · Erasmus MC Hart en Vaat Instituut
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
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Erasmus MC · Erasmus MC Hart en Vaat Instituut
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
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Affiliation as printed
Mimetas B.V. De Limes 7 Oegstgeest 2342 DH The Netherlands
Mimetas B.V., De Limes 7, Oegstgeest, 2342 DH The Netherlands
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Delft University of Technology
Affiliation as printed
Department of Bionanoscience Delft University of Technology Building 58, Van der Maasweg 9 Delft 2629 HZ The Netherlands
Department of Bionanoscience, Delft University of Technology, Building 58, Van der Maasweg 9, Delft, 2629 HZ The Netherlands
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Erasmus MC · Erasmus MC Hart en Vaat Instituut
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
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Delft University of Technology
Affiliation as printed
Department of Bionanoscience Delft University of Technology Building 58, Van der Maasweg 9 Delft 2629 HZ The Netherlands
Department of Bionanoscience, Delft University of Technology, Building 58, Van der Maasweg 9, Delft, 2629 HZ The Netherlands
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Erasmus MC · Erasmus MC Hart en Vaat Instituut · Delft University of Technology
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Department of Imaging Physics Delft University of Technology Building 22, Lorentzweg 1 Delft 2628 CJ The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
Department of Imaging Physics, Delft University of Technology, Building 22, Lorentzweg 1, Delft, 2628 CJ The Netherlands
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Erasmus MC · Erasmus MC Hart en Vaat Instituut · Delft University of Technology
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Department of Imaging Physics Delft University of Technology Building 22, Lorentzweg 1 Delft 2628 CJ The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
Department of Imaging Physics, Delft University of Technology, Building 22, Lorentzweg 1, Delft, 2628 CJ The Netherlands
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Erasmus MC · Erasmus MC Hart en Vaat Instituut · ORTEC (Netherlands)
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Department of Health ORTEC B.V. Houtsingel 5 Zoetermeer 2719 EA The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
Department of Health, ORTEC B.V., Houtsingel 5, Zoetermeer, 2719 EA The Netherlands
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Affiliation as printed
Mimetas B.V. De Limes 7 Oegstgeest 2342 DH The Netherlands
Mimetas B.V., De Limes 7, Oegstgeest, 2342 DH The Netherlands
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Klazina Kooiman corresponding
Erasmus MC · Erasmus MC Hart en Vaat Instituut
Affiliation as printed
Biomedical Engineering Department of Cardiology Cardiovascular Institute Erasmus MC Wytemaweg 80 Rotterdam 3015 CN The Netherlands
Biomedical Engineering, Department of Cardiology, Cardiovascular Institute, Erasmus MC, Wytemaweg 80, Rotterdam, 3015 CN The Netherlands
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