Adaptation of the kirkstall QV600 LLI microfluidics system for the study of gastrointestinal absorption by mass spectrometry imaging and LC-MS/MS

SPENCER, Chloe E., RUMBELOW, Stephen, MELLOR, Steve, DUCKETT, Catherine J. and CLENCH, Malcolm R. (2022). Adaptation of the kirkstall QV600 LLI microfluidics system for the study of gastrointestinal absorption by mass spectrometry imaging and LC-MS/MS. Pharmaceutics, 14 (2).

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Official URL: https://www.mdpi.com/1999-4923/14/2/364
Open Access URL: https://www.mdpi.com/1999-4923/14/2/364/pdf (Published version)
Link to published version:: https://doi.org/10.3390/pharmaceutics14020364
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    Abstract

    Absorption studies on oral drugs can be difficult due to the challenge of replicating the complex structure and environment of the GI tract. Drug absorption studies can be conducted using in vivo and ex vivo animal tissue or animal-free techniques. These studies typically involve the use of Caco-2 cells. However, Caco-2 cells do not incorporate all the cell types found in intestinal tissue and lack P450 metabolizing enzymes. The QV600 LLI system is a microfluidics system designed for use with cell culture. Here, it has been adapted to house appropriate sections of ex vivo porcine tissue to act as a system that models the duodenum section of the small intestine. A pH regulated solution of Atorvastatin was flowed over the apical layer of the GI tissue and a nutrient solution flowed over the basal layer of the tissue to maintain tissue viability. The tissue samples were snap-frozen, cryosectioned, and imaged using MALDI Mass Spectrometry Imaging (MSI). A proof-of-concept study on the effect of excipients on absorption was conducted. Different concentrations of the solubilizing agent were added to the donor circuit of the QV600 LLI. The amount of Atorvastatin in the acceptor circuit was determined to study the effect of the excipient on the amount of drug that had permeated through the tissue. Using these data, Papp, pig values were calculated and compared with the literature.

    Item Type: Article
    Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1999-4923 **History: published 05-02-2022; accepted 02-02-2022
    Uncontrolled Keywords: mass spectrometry imaging, microfluidics, Atorvastatin, polysorbate 80
    Identification Number: https://doi.org/10.3390/pharmaceutics14020364
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 10 Feb 2022 10:35
    Last Modified: 10 Feb 2022 10:45
    URI: http://shura.shu.ac.uk/id/eprint/29705

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