Article ; Online: Biorelevant media resistant co-culture model mimicking permeability of human intestine.
International journal of pharmaceutics
2015 Volume 481, Issue 1-2, Page(s) 27–36
Abstract: Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions ... ...
| Abstract | Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. |
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| MeSH term(s) | ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Biological Transport ; Caco-2 Cells ; Cell Survival ; Coculture Techniques ; HT29 Cells ; Humans ; Intestinal Absorption ; Intestinal Secretions ; Intestines/metabolism ; Mucus/metabolism ; Permeability ; Propranolol/pharmacology | |||||
| Chemical Substances | ATP-Binding Cassette, Sub-Family B, Member 1 ; Propranolol (9Y8NXQ24VQ) | |||||
| Language | English | |||||
| Publishing date | 2015-03-15 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 428962-6 | |||||
| ISSN | 1873-3476 ; 0378-5173 | |||||
| ISSN (online) | 1873-3476 | |||||
| ISSN | 0378-5173 | |||||
| DOI | 10.1016/j.ijpharm.2015.01.028 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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