6533b7dcfe1ef96bd127173a

RESEARCH PRODUCT

Usefulness of Caco-2/HT29-MTX and Caco-2/HT29-MTX/Raji B Coculture Models To Predict Intestinal and Colonic Permeability Compared to Caco-2 Monoculture

Isabel Lozoya-agulloBruno SarmentoMarta González-álvarezMarival BermejoIsabel González-álvarezFrancisca AraújoMatilde Merino-sanjuán

subject

0301 basic medicineDrugColonmedia_common.quotation_subjectPharmaceutical Science02 engineering and technologyBiologydigestive systemPermeability03 medical and health sciencesCell Line TumorDrug DiscoverymedicineLow permeabilityHumansIntestinal Mucosamedia_commonHt29 mtxIntestinal permeability021001 nanoscience & nanotechnologymedicine.diseaseIntestinal epitheliumCoculture Techniques030104 developmental biologyIntestinal AbsorptionCaco-2Cell culturePermeability (electromagnetism)ImmunologyCancer researchMolecular MedicineCaco-2 Cells0210 nano-technologyHT29 Cells

description

The Caco-2 cellular monolayer is a widely accepted in vitro model to predict human permeability but suffering from several and critical limitations. Therefore, some alternative cell cultures to mimic the human intestinal epithelium, as closely as possible, have been developed to achieve more physiological conditions, as the Caco-2/HT29-MTX coculture and the triple Caco-2/HT29-MTX/Raji B models. In this work the permeability of 12 model drugs of different Biopharmaceutical Classification System (BCS) characteristics, in the coculture and triple coculture models was assessed. Additionally, the utility of both models to classify compounds according to the BCS criteria was scrutinized. The obtained results suggested that the coculture of Caco-2/HT29-MTX and the triple coculture of Caco-2/HT29-MTX/Raji B were useful models to predict intestinal permeability and to classify the drugs in high or low permeability according to BCS. Moreover, to study thoroughly the transport mechanism of a specific drug, using a more complex model than Caco-2 monocultures is more suitable because coculture and triple coculture are more physiological models, so the results obtained with them will be closer to those obtained in the human intestine.

https://doi.org/10.1021/acs.molpharmaceut.6b01165