Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux.
Publication year
2024Source
European Journal of Pharmaceutical Sciences, 201, (2024), pp. 106877, article 106877ISSN
Publication type
Article / Letter to editor
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Organization
Pharmacy
Surgery
Medical Biosciences
Intensive Care
Journal title
European Journal of Pharmaceutical Sciences
Volume
vol. 201
Page start
p. 106877
Subject
Intensive Care - Radboud University Medical Center; Medical Biosciences - Radboud University Medical Center; Pharmacy - Radboud University Medical Center; Surgery - Radboud University Medical CenterAbstract
After oral administration, the intestine is the first site of drug absorption, making it a key determinant of the bioavailability of a drug, and hence drug efficacy and safety. Existing non-clinical models of the intestinal barrier in vitro often fail to mimic the barrier and absorption of the human intestine. We explore if human enteroid monolayers are a suitable tool for intestinal absorption studies compared to primary tissue (Ussing chamber) and Caco-2 cells. Bidirectional drug transport was determined in enteroid monolayers, fresh tissue (Ussing chamber methodology) and Caco-2 cells. Apparent permeability (P(app)) and efflux ratios for enalaprilat (paracellular), propranolol (transcellular), talinolol (P-glycoprotein (P-gp)) and rosuvastatin (Breast cancer resistance protein (BCRP)) were determined and compared between all three methodologies and across intestinal regions. Bulk RNA sequencing was performed to compare gene expression between enteroid monolayers and primary tissue. All three models showed functional efflux transport by P-gp and BCRP with higher basolateral to apical (B-to-A) transport compared to apical-to-basolateral (A-to-B). B-to-A P(app) values were similar for talinolol and rosuvastatin in tissue and enteroids. Paracellular transport of enalaprilat was lower and transcellular transport of propranolol was higher in enteroids compared to tissue. Enteroids appeared show more region- specific gene expression compared to tissue. Fresh tissue and enteroid monolayers both show active efflux by P-gp and BCRP in jejunum and ileum. Hence, the use of enteroid monolayers represents a promising and versatile experimental platform to complement current in vitro models.
This item appears in the following Collection(s)
- Academic publications [245132]
- Electronic publications [132441]
- Faculty of Medical Sciences [93207]
- Open Access publications [106000]
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