In vitro 3D human small intestinal villous model for drug permeability determination.

We present a novel method for testing drug permeability that features human cells cultured on hydrogel scaffolds made to accurately replicate the shape and size of human small intestinal villi. We compared villous scaffolds to more conventional 2D cultures in paracellular drug absorption and cell growth experiments. Our results suggest that 3D villous platforms facilitate cellular differentiation and absorption more similar to mammalian intestines than can be achieved using conventional culture. To the best of our knowledge, this is the first accurate 3D villus model offering a well-controlled microenvironment that has strong physiological relevance to the in vivo system.

[1]  K. Luthman,et al.  Caco-2 monolayers in experimental and theoretical predictions of drug transport. , 2001, Advanced drug delivery reviews.

[2]  P. Artursson,et al.  Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. , 1990, Journal of pharmaceutical sciences.

[3]  H. Lennernäs,et al.  Comparison between active and passive drug transport in human intestinal epithelial (Caco-2) cells in vitro and human jejunum in vivo , 1996 .

[4]  Per Artursson,et al.  Intestinal Drug Absorption and Metabolism in Cell Cultures: Caco-2 and Beyond , 1997, Pharmaceutical Research.

[5]  Kristina Luthman,et al.  Caco-2 monolayers in experimental and theoretical predictions of drug transport1PII of original article: S0169-409X(96)00415-2. The article was originally published in Advanced Drug Delivery Reviews 22 (1996) 67–84.1 , 2001 .

[6]  M. Pinto,et al.  Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture , 1983 .

[7]  Thomas J. Raub,et al.  Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. , 1989, Gastroenterology.

[8]  D. Thakker,et al.  Applications of the Caco-2 model in the design and development of orally active drugs: elucidation of biochemical and physical barriers posed by the intestinal epithelium , 1997 .

[9]  P. Artursson,et al.  Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. , 1991, Biochemical and biophysical research communications.

[10]  H. Lennernäs,et al.  Intestinal drug absorption during induced net water absorption in man; a mechanistic study using antipyrine, atenolol and enalaprilat. , 1994, British journal of clinical pharmacology.

[11]  K. Luthman,et al.  Caco-2 monolayers in experimental and theoretical predictions of drug transport , 1996 .

[12]  Elizabeth E. Hoskins,et al.  Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro , 2010, Nature.

[13]  P. Artursson,et al.  Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells. , 1990, Journal of pharmaceutical sciences.

[14]  J. Schulzke,et al.  Epithelial Tight Junction Structure in the Jejunum of Children with Acute and Treated Celiac Sprue , 1998, Pediatric Research.

[15]  Per Artursson,et al.  Selective Paracellular Permeability in Two Models of Intestinal Absorption: Cultured Monolayers of Human Intestinal Epithelial Cells and Rat Intestinal Segments , 1993, Pharmaceutical Research.

[16]  P. Artursson,et al.  Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers , 2007, Nature Protocols.

[17]  Jiajie Yu,et al.  Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. , 2011, Lab on a chip.