Skip to main content

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 8))

Abstract

In vitro systems such as brush border membrane vesicles (BBMV), basolateral membrane vesicles (BLMV), perfused intestinal loops, stripped intestinal mucosa, and isolated enterocytes have been used to study mucosal drug absorption. Isolated enterocytes should permit the determination of transmembrane transport in the presence of cellular metabolism. However, upon isolation enterocytes lose their polarity and show limited viability (Hartmann et al., 1982). Attempts to develop an in vitro system derived from cultured intestinal epithelial cells have found this goal to be extremely difficult. Although intestinal enterocytes have been cultured in suspension, they undergo dedifferentiation when cultured as monolayers (Raul et al., 1978).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Artursson, P., 1990, 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.

    Article  PubMed  CAS  Google Scholar 

  • Artursson, P., and Karlsson, J., 1991, Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells, Biochem. Biophys. Res. Commun. 175:880–885.

    Article  PubMed  CAS  Google Scholar 

  • Audus, K. L., Bartel, R. L., Hidalgo, I. J., and Borchardt, R. T., 1990, The use of cultured epithelial and endothelial cells for drug transport and metabolism studies, Pharm. Res. 7:435–451.

    Article  PubMed  CAS  Google Scholar 

  • Baranczyk-Kuzma, A., Garren, J. A., Hidalgo, I. J., and Borchardt, R. T., 1991, Substrate specificity and some properties of phenol sulfotransferase from human Caco-2 cells, Life Sci. 49:1197–1206.

    Article  PubMed  CAS  Google Scholar 

  • Blais, A., Bissonnette, P., and Berteloot, A., 1987, Common characteristics for Na+-dependent sugar transport in Caco-2 cells and human fetal colon, J. Membr. Biol 99:113–125.

    Article  PubMed  CAS  Google Scholar 

  • Boulenc, X., Bourne, M., Fabre, J., Roque, C., Joyeux, H., Berger, Y., and Fabre, G., 1992, Regulation of cytochrome P4501Al gene expression in a human intestinal cell line, Caco-2, J. Pharmacol. Exp. Ther. 263:1471–1478.

    PubMed  CAS  Google Scholar 

  • Carriere, V., Lesuffleur, T., Barbat, A., Rousset, M., Dussaulx, E., Costet, P., de Waziers, I., Beaune, P., and Zweibaum, A., 1994, Expression of cytochrome P-450 3A in HT29-MTX cells and Caco-2 clone TC7, FEBS Lett. 355:247–250.

    Article  PubMed  CAS  Google Scholar 

  • Dantzig, A. H., and Bergin, L., 1990, Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2, Biochim. Biophys. Acta 1027:211–217.

    Article  PubMed  CAS  Google Scholar 

  • Dix, C. J., Hassan, I. F., Obray, H. Y., Shah, R., and Wilson, G., 1990, The transport of vitamin B12 through polarized monolayers of Caco-2 cells, Gastroenterology 98:1272–1279.

    PubMed  CAS  Google Scholar 

  • Gochoco, C. H., Ryan, F. M., Miller, J., Smith, P. L., and Hidalgo, I. J., 1994, Uptake and transepithelial transport of the orally absorbed cephalosporin cephalexin, in the human intestinal cell line, Caco-2, Int. J. Pharm. 104:187–202.

    Article  CAS  Google Scholar 

  • Hartmann, F., Owen, R., and Bisseil, D. M., 1982, Characterization of isolated epithelial cells from rat small intestine, Am. J. Physiol. 242:G147–G155.

    PubMed  CAS  Google Scholar 

  • Hidalgo, I. J., and Borchardt, R. T., 1990a, Transport of a large neutral amino acid (phenylalanine) in a human intestinal epithelial cell line: Caco-2, Biochim. Biophys. Acta 1035:25–30.

    Article  Google Scholar 

  • Hidalgo, I. J., and Borchardt, R. T., 1990b, Transport of bile acids in a human intestinal epithelial cell line, Caco-2, Biochim. Biophys. Acta 1035:97–103.

    Article  PubMed  CAS  Google Scholar 

  • Hidalgo, I. J., Raub, T. J., and Borchardt, R. T., 1989, Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability, Gastroenterology 96:736–749.

    PubMed  CAS  Google Scholar 

  • Hidalgo, I. J., Hillgren, K. M., Grass, G. M., and Borchardt, R. T, 1991, Characterization of the unstirred water layer in Caco-2 cell monolayers using a novel diffusion apparatus, Pharm. Res. 8:222–227.

    Article  PubMed  CAS  Google Scholar 

  • Hidalgo, I. J., Hillgren, K. M., Grass, G. M., and Borchardt, R. T., 1992, A new side-by-side diffusion cell for studying transport across epithelial cell monolayers, In Vitro Cell. Dev. Biol. 28A:578–580.

    CAS  Google Scholar 

  • Hunter, J., Jepson, M. A., Tsuruo, T., Simmons, N. L., and Hirst, B. H., 1993, Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells: Kinetics of vinblastine secretion and interactions with modulators, J. Biol. Chem. 268:14991–14997.

    PubMed  CAS  Google Scholar 

  • Inui, K.-I., Yamamoto, M., and Saito, H., 1992, Transepithelial transport of oral cephalosporins by monolayers of intestinal epithelial cell line Caco-2: Specific transport systems in apical and basolateral membranes, J. Pharmacol. Exp. Ther. 261:195–201.

    PubMed  CAS  Google Scholar 

  • Kim, D.-C., Harrison, A. W., Ruwart, M. J., Wilkinson, K. F., Fisher, J. F., Hidalgo, I. J., and Borchardt, R. T., 1993, Evaluation of the bile acid transporter in enhancing intestinal permeability to renin-inhibitory peptides, J. Drug Targeting 1:347–359.

    Article  CAS  Google Scholar 

  • Lesuffleur, T., Porchet, N., Aubert, J.-P., Swallow, D., Gum, J. R., Kim, Y. S., Real, F. X., and Zweibaum, A., 1993, Differential expression of the human mucin genes MUC1 to MUC5 in relation to growth and differentiation of different mucus-secreting HT-29 cell sub populations, J. Cell Sci. 106:771–783.

    PubMed  CAS  Google Scholar 

  • Lown, K. S., Kolars, J. C., Thummel, K. E., Barnett, J. L., Kunze, K. L., Wrighton, S. A., and Watkins, P. B., 1994, Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breadth test, Drug Metab. Dispos. 22:947–955.

    PubMed  CAS  Google Scholar 

  • Madara, J. L., Stafford, J., Barenberg, D., and Carlson, S., 1988, Functional coupling of tight junctions and microfilaments in T84 monolayers, Am. J. Physiol. 254:G416–G423.

    PubMed  CAS  Google Scholar 

  • Ng, K.-Y., and Borchardt, R. T., 1993, Biotin transport in a human intestinal epithelial cell line (Caco-2), Life Sci. 53:1121–1127.

    Article  PubMed  CAS  Google Scholar 

  • Nicklin, P., Irwin, B., Hassan, I., Williamson, I., and Mackay, M., 1992, Permeable support type influences the transport of compounds across Caco-2 cells, Int. J. Pharm. 83:197–209.

    Article  CAS  Google Scholar 

  • Pinto, M., Robine-Leon, S., Appay, M. D., Kedinger, M., Triadou, N., Dussaulx, E., Lacroix, B., Simon-Assmann, P., Haffen, K., Fogh, J. and Zweibaum, A., 1983, Enterocytic-like differentiation and polarization of the human colon adenocarcinoma cell line Caco-2 in culture, Biol. Cell. 47:323–330.

    Google Scholar 

  • Ranaldi, G., Islam, K., and Sambuy, Y., 1992, Epithelial cells in culture as a model for the intestinal transport of antimicrobial agents, Antimicrob. Agents Chemother. 36:1374–1381.

    Article  PubMed  CAS  Google Scholar 

  • Raul, F., Kedinger, M., Simon, P., Grenier, J., and Haffen, K., 1978, Behaviour of isolated rat intestinal cell maintained in suspension or monolayer cultures, Biol. Cell 33:163–168.

    CAS  Google Scholar 

  • Segel, I. H., 1976, Biochemical Calculation, Wiley & Sons, New York, p. 252.

    Google Scholar 

  • Sugawara, M., Saitoh, H., Iseki, K., Miyazaki, K., and Arita, T., 1990, Contribution of passive transport mechanisms to the intestinal absorption of β-lactam antibiotics, J. Pharm. Pharmacol. 42:314–318.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, A. B. R., and Dietschy, J. M., 1980, Experimental demonstration of the effect of the unstirred water layer on the kinetic constants of the membrane transport of D-glucose in rabbit jejunum, J. Membr. Biol. 54:221–229.

    Article  PubMed  CAS  Google Scholar 

  • Vincent, M. L., Russell, R. M., and Sasak, V., 1985, Folic acid uptake characteristics of a human colon carcinoma cell line, Caco-2. A newly described cellular model for small intestinal epithelium, Hum. Nutr. Clin. Nutr. 39C:355–360.

    Google Scholar 

  • Yamashita, S., Yamazaki, Y., Mizuno, M., Masada, M., Nadai, T., Kimura, T., and Sezaki, H., 1984, Further investigations on the transport mechanism of cephalexin and ampicillin across rat jejunum, J. Pharmacobio-Dyn. 7:227–233.

    Article  PubMed  CAS  Google Scholar 

  • Zweibaum, A., Triadou, N., Kedinger, M., Augeron, C., Robine-Leon, S., Pinto, M., Rousset, M., and Haffen, K., 1983, Sucrase-isomaltase: A marker of foetal and malignant epithelial cells of the human colon, Int. J. Cancer 32:407–412.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hidalgo, I.J. (1996). Cultured Intestinal Epithelial Cell Models. In: Borchardt, R.T., Smith, P.L., Wilson, G. (eds) Models for Assessing Drug Absorption and Metabolism. Pharmaceutical Biotechnology, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1863-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-1863-5_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1865-9

  • Online ISBN: 978-1-4899-1863-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics