Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging
| Autor: | Christian Janfelt, Sophie Strindberg, Charlotte Bagger, Jakob Plum, Anette Müllertz |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Administration Oral Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Mass spectrometry imaging 03 medical and health sciences 0302 clinical medicine Fenofibrate Suspensions In vivo Drug Discovery medicine Animals Distribution (pharmacology) Prodrugs Tissue Distribution Spatial Analysis Gastrointestinal tract Chromatography Chemistry Prodrug 021001 nanoscience & nanotechnology Small intestine Molecular Imaging Rats Gastrointestinal Tract Matrix-assisted laser desorption/ionization medicine.anatomical_structure Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Models Animal Molecular Medicine 0210 nano-technology medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 18:2189-2197 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|