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Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors

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dc.contributor Aalto-yliopisto fi
dc.contributor Aalto University en
dc.contributor.author Kiiski, Iiro
dc.contributor.author Ollikainen, Elisa
dc.contributor.author Artes, Sanna
dc.contributor.author Järvinen, Päivi
dc.contributor.author Jokinen, Ville
dc.contributor.author Sikanen, Tiina
dc.date.accessioned 2020-12-31T08:40:19Z
dc.date.available 2020-12-31T08:40:19Z
dc.date.issued 2021-03-01
dc.identifier.citation Kiiski , I , Ollikainen , E , Artes , S , Järvinen , P , Jokinen , V & Sikanen , T 2021 , ' Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors ' , European Journal of Pharmaceutical Sciences , vol. 158 , 105677 . https://doi.org/10.1016/j.ejps.2020.105677 en
dc.identifier.issn 0928-0987
dc.identifier.other PURE UUID: 42067720-88b8-4474-86e1-a36dbdee85e0
dc.identifier.other PURE ITEMURL: https://research.aalto.fi/en/publications/drug-glucuronidation-assays-on-human-liver-microsomes-immobilized-on-microfluidic-flowthrough-reactors(42067720-88b8-4474-86e1-a36dbdee85e0).html
dc.identifier.other PURE LINK: http://www.scopus.com/inward/record.url?scp=85097791691&partnerID=8YFLogxK
dc.identifier.other PURE FILEURL: https://research.aalto.fi/files/54444250/1_s2.0_S0928098720304656_main.pdf
dc.identifier.uri https://aaltodoc.aalto.fi/handle/123456789/101467
dc.description.abstract UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family of enzymes, responsible for the biotransformation of several endogenous and exogenous chemicals, including therapeutic drugs. However, the phenomenon of ‘latency’, i.e., full UGT activity revealed by disruption of the microsomal membrane, poses substantial challenges for predicting drug clearance based on in vitro glucuronidation assays. This work introduces a microfluidic reactor design comprising immobilized human liver microsomes to facilitate the study of UGT-mediated drug clearance under flow-through conditions. The performance of the microreactor is characterized using glucuronidation of 8-hydroxyquinoline (via multiple UGTs) and zidovudine (via UGT2B7) as the model reactions. With the help of alamethicin and albumin effects, we show that conducting UGT metabolism assays under flow conditions facilitates in-depth mechanistic studies, which may also shed light on UGT latency. en
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Elsevier Science B.V.
dc.relation.ispartofseries European Journal of Pharmaceutical Sciences en
dc.relation.ispartofseries Volume 158 en
dc.rights openAccess en
dc.subject.other Pharmaceutical Science en
dc.subject.other 116 Chemical sciences en
dc.title Drug glucuronidation assays on human liver microsomes immobilized on microfluidic flow-through reactors en
dc.type A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä fi
dc.description.version Peer reviewed en
dc.contributor.department University of Helsinki
dc.contributor.department Department of Chemistry and Materials Science
dc.contributor.department Department of Chemistry and Materials Science en
dc.subject.keyword Drug metabolism
dc.subject.keyword Enzyme immobilization
dc.subject.keyword Glucuronidation
dc.subject.keyword Microfabrication
dc.subject.keyword Microfluidics
dc.subject.keyword Microreactors
dc.subject.keyword Pharmaceutical Science
dc.subject.keyword 116 Chemical sciences
dc.identifier.urn URN:NBN:fi:aalto-2020123160288
dc.identifier.doi 10.1016/j.ejps.2020.105677
dc.type.version publishedVersion

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