Fabrication of multilayer heterogeneous cell assembly for pathophysiologically relevant 3Din-vitroIBD disease model for high throughput drug screening.

Abstract

Regarding the approval of novel pharmaceuticals, the most common reason for failure is inadequate oral drug bioavailability. Owing to the complex physiological milieu of the human intestine, which is characterized by its varied composition, various functions, and one-of-a-kind dynamic conditions, it is difficult to reproduce the organin vitro. Traditional monolayers in two dimensions, sophisticated three-dimensional systems, and developing fluid-dynamic platforms are examples ofin-vitrointestinal models. Caco-2 cells have been the gold standard for studying drug permeability for over two decades, particularly for BCS Class II/III/IV drugs. Other intestinalin vitromodels exist; however, pharmaceutical corporations and regulatory authorities use the Caco-2 cell line to predict human intestinal permeability. To predict oral drug absorption and study normal intestinal epithelial physiology, it is necessary to have advanced technologies capable of creating human intestinal epithelial cells (hIECs) with cellular variety and functions. There is a strong link between the permeability data obtainedin vitroand the fractions absorbed by humans in complex multicellular models. However, although microphysiological systems accurately replicate physiological cues of the digestive tract, they still require standardization. We critically reviewed a step towards tissue-created 3D intestinal organoids and 3D heterocellular multicompartmental models without compromising cellular variety and function. To bridge the gap between 2D and 3D intestinal culture models, a physiologically appropriate hIEC model provides a novel platform for patient-specific testing and translational applications. A comprehensive understanding of numerous 3Din-vitromodels of inflammatory bowel disease has been discussed. Additionally, this review will provide insights into the benefits and limitations of these models and their relevance in understanding intestinal physiology and accelerating drug discovery through high-throughput screening.