Joseph Leedale -- Multiscale modelling of drug transport and metabolism in liver spheroids
|Starts:||14:00 15 Nov 2021|
|Ends:||14:00 15 Nov 2021|
|What is it:||Seminar|
|Organiser:||Department of Mathematics|
|Who is it for:||University staff, External researchers, Current University students|
Join us for this seminar by Joe Leedale (formerly Liverpool, now at Syngenta) as part of the North West Seminar Series in Mathematical Biology and Data Sciences. Details of the full series can be found here https://www.cms.livjm.ac.uk/APMSeminar/.
The talk will be hosted via zoom. Participants can also join via zoom, please contact firstname.lastname@example.org or email@example.com for the zoom link, or sign up to the mailing list.
Abstract: In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. These in-vitro experiments traditionally involve cells cultured in a two-dimensional monolayer environment. However, cells cultured in three-dimensional spheroid systems have been shown to more closely resemble the functionality and morphology of cells in-vivo. While the increasing usage of hepatic spheroid cultures allows for more relevant experimentation in a more realistic biological environment, the underlying physical processes of drug transport, uptake and metabolism contributing to the spatial distribution of drugs in these spheroids remain poorly understood. The development of a multiscale mathematical modelling framework describing the spatiotemporal dynamics of drugs in multicellular environments enables mechanistic insight into the behaviour of these systems. Here, our analysis of cell membrane permeation and porosity throughout the spheroid reveals the impact of these properties on drug penetration, with maximal disparity between zonal metabolism rates occurring for drugs of intermediate lipophilicity. Our research shows how mathematical models can be used to simulate the activity and transport of drugs in hepatic spheroids, and in principle any organoid, with the ultimate aim of better informing experimentalists on how to regulate dosing and culture conditions to more effectively optimise drug delivery.
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Role: Technical expert, product safety
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