Caco2solumallit

Caco-2 solumallit, or Caco-2 cell models, are in vitro models of the human intestinal epithelium derived from a colorectal adenocarcinoma cell line. When cultured on permeable inserts, Caco-2 cells differentiate into a polarized monolayer with tight junctions, microvilli and brush-border enzymes, closely resembling enterocytes of the small intestine. They are widely used to study oral drug absorption, intestinal permeability and transporter activity.

Typical setup involves growing cells on Transwell inserts, creating distinct apical and basolateral compartments. Barrier integrity is monitored by transepithelial electrical resistance (TEER). After about 14–21 days of differentiation, the monolayers express uptake and efflux transporters such as PEPT1 and MDR1 (P-glycoprotein) and exhibit functional tight junctions. Enzymatic activity is present but generally lower than in native small intestine, with limited expression of certain enzymes like CYP3A4, which can affect metabolism studies. Permeability is quantified using apparent permeability coefficients (Papp) to predict oral absorption.

Applications and enhancements: Caco-2 models are used to screen drug permeability, predict oral bioavailability and support formulation strategies. To better mimic the intestinal environment, co-culture variants such as Caco-2/HT29-MTX introduce mucus-producing cells, creating a mucus layer. Microfluidic organ-on-a-chip systems and three-dimensional cultures add shear stress and architecture that more closely resemble in vivo conditions.

Limitations: They do not fully replicate the complexity of the in vivo intestine, lacking microbiota and dynamic physiological cues, and show donor-to-donor variability and limited enzymatic activity. Consequently, results are often integrated with other models and in vivo data for comprehensive assessment.