Su124 HOMOLOGY DIRECTED REPAIR IN CANINE DUODENAL ENTEROIDS TO MIMIC THE WILD-TYPE P-GLYCOPROTEIN MUTATION

Zdyrski, Christopher; Iennarella-Servantez, Chelsea A.; Sahoo, Dipak Kumar; Ward, John L.; Long, Elizabeth M.; Gabriel, Vojtěch; Minkler, Sarah; Mao, Sichao; Bourgois-Mochel, Agnes; Jergens, Albert E.; Allenspach, Karin; Mochel, Jonathan P.

doi:10.1016/s0016-5085(21)02200-9

Cited by 2 publications

(2 citation statements)

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“…Research in biomedical science, disease modeling, and personalized medicine has advanced since Sato et al (2009) first reported the in vitro culture of intestinal organoids [19,[29][30][31][32][33][34][35][36][37][38][39]. Three-dimensional (3D) organoids are derived from leucine-rich repeat containing G-proteincoupled receptor 5 (Lgr5)-positive adult stem cells [35,38,39].…”

Section: Figurementioning

confidence: 99%

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Sahoo

Martinez

Dao

et al. 2023

Cells

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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 canine-colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both the absorptive and secretive apparent permeability (Papp) 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.

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Section: Figurementioning

confidence: 99%

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Sahoo

Martinez

Dao

et al. 2023

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Research in biomedical science, disease modeling, and personalized medicine has advanced since Sato et al (2009) first reported the in vitro culture of intestinal organoids [19,[29][30][31][32][33][34][35][36][37][38][39]. Three-dimensional (3D) organoids are derived from leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5)-positive adult stem cells [35,38,39].…”

Section: Introductionmentioning

confidence: 99%

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Sahoo¹,

Martinez²,

Dao³

et al. 2023

Preprint

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A key component of efforts to identify the biological and drug-specific aspects that contribute 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, there is relatively little information available for similar evaluation 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 the development of 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 canine colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine colonoid-derived monolayers and were 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.

show abstract

Su124 HOMOLOGY DIRECTED REPAIR IN CANINE DUODENAL ENTEROIDS TO MIMIC THE WILD-TYPE P-GLYCOPROTEIN MUTATION

Cited by 2 publications

References 0 publications

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

Canine Intestinal Organoids as a Novel In Vitro Model of Intestinal Drug Permeability: A Proof-of-Concept Study

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