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Open AccessArticle

Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor

Research Center “E. Piaggio”, University of Pisa, 56122 Pisa, Italy
LARF-DIMES, Department of Experimental Medicine, University of Genoa, 16126 Genoa, Italy
Centro 3R (Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research), 56122 Pisa, Italy
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Bioengineering 2020, 7(3), 100;
Received: 31 July 2020 / Revised: 14 August 2020 / Accepted: 18 August 2020 / Published: 26 August 2020
Multidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can efficiently inhibit P-gp activity remains a challenge, nevertheless some studies have identified natural compounds suitable for that purpose. Amongst them, curcumin has shown an inhibitory effect on the protein in in vitro studies using Caco-2 cells. To understand if flow can modulate the influence of curcumin on the protein’s activity, we studied the uptake of a P-gp substrate under static and dynamic conditions. Caco-2 cells were cultured in bioreactors and in Transwells and the basolateral transport of rhodamine-123 was assessed in the two systems as a function of the P-gp activity. Experiments were performed with and without pre-treatment of the cells with an extract of curcumin or an arylmethyloxy-phenyl derivative to evaluate the inhibitory effect of the natural substance with respect to a synthetic compound. The results indicated that the P-gp activity of the cells cultured in the bioreactors was intrinsically lower, and that the effect of both natural and synthetic inhibitors was up modulated by the presence of flow. Our study underlies the fact that the use of more sophisticated and physiologically relevant in vitro models can bring new insights on the therapeutic effects of natural substances such as curcumin. View Full-Text
Keywords: curcumin; Caco-2 cells; fluidic systems; P-gp modulation; bioreactors; intestinal in-vitro models curcumin; Caco-2 cells; fluidic systems; P-gp modulation; bioreactors; intestinal in-vitro models
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Costa, J.; Almonti, V.; Cacopardo, L.; Poli, D.; Rapposelli, S.; Ahluwalia, A. Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor. Bioengineering 2020, 7, 100.

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