Intestinal cell culture model

The solutes for which transport was evaluated in the IPL were also assayed for their transport in epithelial cell culture models. Permeability in the Caco-2 intestinal cell culture model [141] and the 16HBE14o- airway cell culture model [81] correlated with the rate of absorption in the IPL, with correlation coefficients of r = 0.96 and r2 = 0.78 respectively. 

Sambruy Y, Ferruzza S, Ranaldi G, De Angelis I (2001) Intestinal cell culture models. Applications in toxicology and pharmacology. Cell Biol Toxicol 17 301— 317. 

Despite the availability of other cell lines, Caco-2 cells remain the most widely used intestinal cell culture model at present. This model has provided valuable information necessary for lead optimization in the drug discovery process. However, it is important to understand that compounds with high permeability in this model are typically well absorbed, whereas compounds with low solubility and low permeability in this model may not necessarily be poorly absorbed in vivo. Although this type of positive selection limits the usefulness in providing a structure-permeability relationship, the Caco-2 model has the most effect in drug discovery when the screen is implemented early and in conjunction with other types of in vitro and in vivo permeability/absorption screens. 

Intestinal cell culture models. European Journal of Pharmaceutical Sciences, 2,... 

Quaroni A. and J. Hochmarm, 1996. Development of intestinal cell culture models for drug transport and metabolism studies. Adv. Drug Deliv. Rev. 22, 3-52. 

LIU Y and HU m (2002) Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perfused rat intestinal model. Drug Metab Dispos. 30 (4) 370-77. 

In this model, no attempt is made to reproduce the in vivo physiochemical conditions occurring in the lumen of the human small intestine during digestion. This cell culture model only provides information about the intestinal absorption and metabolism processes of the compound. Using this cell culture system in con-... 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

Kim DC, PS Burton, RT Borchardt. (1993). A correlation between the permeability characteristics of a series of peptides using an in vitro cell culture model (Caco-2) and those using an in situ perfused rat ileum model of the intestinal mucosa. Pharm Res 10 1710-1714. 

Tavelin, S., J. Taipalensuu, F. Hallbook, K. Vellonen, V. Moore, and P. Artursson. An Improved Cell Culture Model Based on 2/4/A1 Cell Monolayers for Studies of Intestinal Drug Transport. Characterization of Transport Routes., Pharm. Res. 2003, 20, 373-381. 

Ingels F, Deferme S, Destexhe E, Oth M, Van den Mooter G, Augustijns P (2002) Simulated intestinal fluid as transport medium in the Caco-2 cell culture model. Int JPharm 232 183-192. 

Tavelin S, Taipalensuu J, Hallbook F, Vellonen KS, Moore V, Artursson P (2003a) An improved cell culture model based on 2/4/A1 cell monolayers for studies of intestinal drug transport Characterization of transport routes. Pharm Res 20 373-381. 

Ungell AL (2002) Transport studies using intestinal tissue ex vivo. In Lehr CM (Ed) Cell Culture Models of Biological Barriers. Taylor and Francis, London, pp 164-188. 

Biganzoli E, Cavenaghi LA, Rossi R, Brunati MC, Nolli ML (1999) Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics. Farmaco 54 594-599. 

There are a number of cell culture models available that mimic human epitheha in vivo (Caco-2, HT29, T84, lEC 18, TC7, LLCPKl, MDCK). Some of these cells are derived from human colon carcinomas (e.g., Caco-2, T84, HT29) and have many properties of the normal intestinal epithelium. The Caco-2 cell model is one of the... 

Troutman MD, Thakker DR. Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res 2003 20(8) 1210-1224. 

Chen W, Tang F, Horie K, Borchardt RT (2002) CACO-2 cell monolayers as a model for studies of drug transport across human intestinal epithelium. In Lehr, KM (ed) Cell Culture models of biological barriers. Taylor and Francis, New York, pp 143-163... 

Liu, Y. and Hu, M., Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model. Drug Metab. Dispos., 30, 370, 2002. Sfakianos, J., Coward, L., Kirk, M. and Barnes, S., Intestinal uptake and biliary excretion of the isoflavone genistein in the rat, J. Nutr., 127, 1260, 1997. 

The advantage of cell culture models is that they are able to measure active transport processes across the cell membranes and not just the interaction of a drug with a lipid bilayer. They can also be used to study passive and active transport routes indeed, much of the knowledge as to the active transport mechanisms in the intestine has been derived from cell culture studies. Despite the predominant route being passive diffusion, the research into transport mechanisms indicates that there are a large number of drugs that are used as substrates for active transporter and efflux systems, and it must therefore be appreciated that multiple transport routes may be involved in the intestinal drug transport. 

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