Caco-2 models absorption

Caco-2 cells and isolated small intestine are models of basic nutrition that contributed to the understanding of resveratrol absorption and bioavailability. While the Caco-2 absorption model is a well-defined cellular in vitro system based on a human colonic adenocarcinoma cell line, the isolated small intestine model is nearer to in vivo conditions and is also simpler to handle. It also avoids the methodological problems of in vivo perfusion models [Barthe et al., 1998, 1999]. 

A number of in vitro systems to model absorption have been developed and have gained widespread use through their successful prediction of human absorption. These include the Caco-2 cell monolayer model, Ussing chambers... 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Taylor, E.W., Giboons, J.A., and Baeck-man, R.A. Intestinal absorption screening of mixtures from combinatorial libraries in the Caco-2 model. Pharm. Res. 1997, 14, 572-577. 

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 contrast to previous in vivo models, this in vitro model provides the possibility of dissociating experimentally two important processes of intestinal absorption cellular uptake and secretion. Under conditions mimicking the postprandial state (taurocholate/oleic acid supplementation), differentiated Caco-2 cells were able to (1) take up carotenoids at the apical sides and incorporate them into CMs and (2) secrete them at the basolateral sides associated with CM fractions. Using this approach, the extent of absorption of P-carotene through Caco-2 cell monolayers after 16 hr of incubation was 11.2%, a value falling within the in vivo range (9 to 22%). ° - Of the total amount of P-carotene secreted, 78% was associated with the two CM fractions and 10% with the VLDL fraction. ... 

The importance of drug ionization using cell-based methods such as Caco-2 in the in vitro prediction of in vivo absorption was discussed [45]. It was observed that when the apical pH used in Caco-2 studies was lowered from 7.4 to 6.0 a better correlation was obtained with in vivo data, demonstrating that careful selection of experimental conditions in vitro is crucial to produce a reUable model. Studies with Caco-2 monolayers also suggested that the ionic species might contribute considerably to overall drug transport [46]. 

Since experimental determination of intestinal absorption is quite demanding, Caco-2 cell monolayers have been successfully used to model passive drug absorption. Several models for the prediction of Caco-2 permeability using PSA were developed, including those of van de Waterbeemd et al. [5] and Palm et al. [22] who found that relationships between Caco-2 permeability and PSA is stronger than with Clog D, Krarup et al. [23] who used dynamic PSA calculated for water accessible molecular surface and Bergstrom et al. [24]. 

Caco-2 Models for Prediction of Human Intestinal Absorption (HIA)... 

Artursson, R, Epithelial transport of drugs in cell culture. I A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells, J. Pharm. Sci. 79, 476-482 (1990). 

Krishna, G. Chen, K.-J. Lin, C.-C. Nomeir, A. A., Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2, Int. J. Pharm. 222, 77-89 (2001). 

Pontier, C. Pachot, J. Botham, R. Lefant, B. Amaud, R, HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption Role of mucus layer, J. Pharm. Sci. 90, 1608-1619 (2001). 

Collett, A. Sims, E. Walker, D. He, Y.-L. Ayrton, J. Rowland, M. Warhurst, G., Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption, Pharm. Res. 13, 216-221 (1996). 

THE HUMAN CACO-2 INTESTINAL CELL MODEL A VALUABLE TOOL FOR STUDYING CAROTENOID ABSORPTION... 

In conclusion, the Caco-2 cell monolayer model has given original data on the competition effect of several nutrients on carotenoid uptake. Most of these data have been confirmed in several in vivo studies, including clinical studies, confirming that this model is a valuable tool to study competition effects on carotenoid absorption. 

Carotenoids are highly lipophilic an active area of research concerns how carotenoids interact with and affect membrane systems (see Chapters 2 and 10). Also, the lipid solubility of these compounds has important implications for carotenoid intestinal absorption (see Chapter 17) models such as the Caco-2 cell model are being used to conduct detailed studies of carotenoid absorption/ competition for absorption (Chapter 18). The lipid solubility of these carotenoids also leads to the aggregation of carotenoids (see Chapter 3). Carotenoids aggregate both in natural and artificial systems, with implications for carotenoid excited states (see Chapter 8). This has implications for a new indication for carotenoids, namely, serving as potential materials for harnessing solar energy. 

More than a decade ago, Caco-2 cells grown on permeable supports were introduced as an experimental tool for mechanistic studies of intestinal drug transport [1-4]. At the same time it was suggested that the Caco-2 model was suitable for screening intestinal drug permeability and predicting the oral absorption potential... 

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