<div class="csl-bib-body">
<div class="csl-entry">Eilenberger, C., Rothbauer, M., Selinger, F., Gerhartl, A., Jordan, C., Harasek, M., Schädl, B., Grillari, J., Weghuber, J., Neuhaus, W., Küpcü, S., & Ertl, P. (2021). A Microfluidic Multisize Spheroid Array for Multiparametric Screening of Anticancer Drugs and Blood-Brain Barrier Transport Properties. <i>Advanced Science</i>, <i>8</i>(11), 2004856. https://doi.org/10.1002/advs.202004856</div>
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dc.identifier.issn
2198-3844
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/138360
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dc.description.abstract
Physiological-relevant in vitro tissue models with their promise of better predictability have the potential to improve drug screening outcomes in preclinical studies. Despite the advances of spheroid models in pharmaceutical screening applications, variations in spheroid size and consequential altered cell responses often lead to nonreproducible and unpredictable results. Here, a microfluidic multisize spheroid array is established and characterized using liver, lung, colon, and skin cells as well as a triple-culture model of the blood-brain barrier (BBB) to assess the effects of spheroid size on (a) anticancer drug toxicity and (b) compound penetration across an advanced BBB model. The reproducible on-chip generation of 360 spheroids of five dimensions on a well-plate format using an integrated microlens technology is demonstrated. While spheroid size-related IC50 values vary up to 160% using the anticancer drugs cisplatin (CIS) or doxorubicin (DOX), reduced CIS:DOX drug dose combinations eliminate all lung microtumors independent of their sizes. A further application includes optimizing cell seeding ratios and size-dependent compound uptake studies in a perfused BBB model. Generally, smaller BBB-spheroids reveal an 80% higher compound penetration than larger spheroids while verifying the BBB opening effect of mannitol and a spheroid size-related modulation on paracellular transport properties.
en
dc.language.iso
en
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dc.publisher
WILEY
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dc.relation.ispartof
Advanced Science
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dc.subject
microfluidics
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dc.subject
General Engineering
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dc.subject
General Materials Science
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dc.subject
General Physics and Astronomy
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dc.subject
General Chemical Engineering
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dc.subject
Biochemistry, Genetics and Molecular Biology (miscellaneous)
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dc.subject
Medicine (miscellaneous)
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dc.subject
anticancer drugs
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dc.subject
blood-brain barrier
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dc.subject
in vitro tests
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dc.subject
multicellular spheroids
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dc.title
A Microfluidic Multisize Spheroid Array for Multiparametric Screening of Anticancer Drugs and Blood-Brain Barrier Transport Properties
en
dc.type
Artikel
de
dc.type
Article
en
dc.description.startpage
2004856
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dc.type.category
Original Research Article
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tuw.container.volume
8
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tuw.container.issue
11
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tuw.journal.peerreviewed
true
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tuw.peerreviewed
true
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tuw.researchTopic.id
X1
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tuw.researchTopic.name
außerhalb der gesamtuniversitären Forschungsschwerpunkte