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

Abstract

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.

A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease

“…Ultimately, this confirms the activation of our bacteria in response to biologically produced NO with a relevant model using intestinal epithelial cells. Further studies should include the use of HT29‐MTX cells in co‐culture with Caco‐2, however, to better mimic the native intestinal lumen; the model would include the mucus barrier, which may interfere with the NO release kinetics and thus GM‐CSF secretion …”

“…Further studies should include the use of HT29-MTX cells in co-culture with Caco-2, however, to better mimic the native intestinal lumen; the model would include the mucus barrier, which may interfere with the NO release kinetics and thus GM-CSF secretion. 98…”

Models of the Gut for Analyzing the Impact of Food and Drugs

“…The co‐culture ratio often used is 90% of Caco‐2 and 10% of HT29‐MTX, but other studies have been conducted at other physiological ratios, such as 75% of Caco‐2 and 25% of HT29‐MTX . Other studies have explored the potential of employing additional cell lines, such as Raji B . The goal of such endeavors is to optimize the mucin layer, which has a significant effect even in promoting bacterial adhesion to the epithelium in vitro .…”

The role of mucus in cell-based models used to screen mucosal drug delivery

“…Using external sources of mucus may further abbreviate changes induced to cell monolayer tightness by the incorporation of cell types presenting different abilities to establish intercellular interactions. For example, our group has recently shown that various drugs present increased permeability across Caco-2/HT29-MTX co-culture cell monolayers as compared to Caco-2 cell monolayers [131]. These observations have been justified with the reduced ability of mucus-producing cells to establish tight-junctions thus leading to a leaky cell monolayer.…”