卷:12 | |
Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study | |
Article | |
关键词: CACO-2 CELLS; STEM-CELLS; EXPRESSION; CULTURE; URINE; CLASSIFICATION; PERMEATION; METOPROLOL; MONOLAYER; BARRIER; | |
DOI : 10.3390/cells12091269 | |
来源: SCIE |
【 摘 要 】
A key component of efforts to identify the biological and drug-specific aspects contributing to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, relatively little information is available for similar evaluations in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in developing such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine-colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this caninecolonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed beta-blockers (e.g., propranolol, metoprolol, and atenolol). Both the absorptive and secretive apparent permeability (P-app) of these drugs at two different pH conditions were evaluated in canine-colonoid-derived monolayers and compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.
【 授权许可】