Forskning ved Københavns Universitet - Københavns Universitet


Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging

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Mapping the spatial distribution of a drug throughout the gastrointestinal tract (GIT) after oral ingestion can provide novel insights into the interaction between the drug, the oral drug delivery system, and the GIT. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a molecular imaging technique that can analyze molecules in the cryosections of tissues, determining their localization with a spatial resolution of 10-100 μm. The overall aim of this study was to use MALDI-MSI to visualize the distribution and spatial location of a model prodrug (fenofibrate) through the rat GIT. Furthermore, the distribution and spatial colocalization of taurocholate and phospholipids in the rat GIT in relation to fenofibrate were investigated. Rats were given a fenofibrate suspension of 10 mg/mL by oral gavage. Blood samples were drawn, and the rats were euthanized at three different time points. The GIT was collected and frozen, and MALDI-MSI was applied on cross sections of the stomach and intestine. Fenofibrate was detected by MALDI-MSI throughout the GIT, which also revealed that fenofibrate was hydrolyzed to the active drug fenofibric acid already in the stomach. Furthermore, the presence of lyso-phosphatidylcholine (lyso-PC) and taurocholate was confirmed in the lumen of the small intestine. MALDI-MSI was shown to be a useful qualitative tool for localizing parent prodrugs and active drugs, with a possibility for gaining insight into not only the location for activation but also the role of endogenous molecules in the process.

TidsskriftMolecular Pharmaceutics
Udgave nummer6
Sider (fra-til)2189–2197
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The support from the Carlsberg Foundation and the Danish Council for Independent Research | Medical Sciences (grant no. DFF–4002-00391) is gratefully acknowledged. Furthermore, the Danish National Research Foundation (Project DNRF122) and Villum Foundation’s Center (Grant No. 9301) for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN) is acknowledged. J.P. is partly funded by the Innovation Fund Denmark (IFD) under File No. 8054-00056B.

Publisher Copyright:
© 2021 American Chemical Society.

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