Role of Caco‐2 Cell Monolayers in Prediction of Intestinal Drug Absorption

The usefulness of Caco‐2 cell monolayers in determining the intestinal drug absorption of potential drug candidates as such and from delivery systems, elucidating the underlying mechanisms thereof, presystemic metabolism, cellular uptake and cytotoxicological assessment has been exemplified in this review. The role of Caco‐2 cell monolayers in studying the effectiveness, involved mechanism and toxicity of various excipients for drug absorption promotion has also been discussed.

[1]  J. Polli,et al.  Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system , 1999, AAPS PharmSci.

[2]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[3]  O. H. Chan,et al.  Comparison of Intestinal Permeabilities Determined in Multiple in Vitro and inSitu Models: Relationship to Absorption in Humans , 1995, Pharmaceutical Research.

[4]  P. Artursson,et al.  The mucus layer as a barrier to drug absorption in monolayers of human intestinal epithelial HT29-H goblet cells , 1993 .

[5]  P. Artursson,et al.  Intestinal tissue distribution and epithelial transport of the oral immunogen LTB, the B subunit of E. coli heat-labile enterotoxin. , 1993, Journal of drug targeting.

[6]  S. Chong,et al.  Cell culture-based models for intestinal permeability: a critique. , 2005, Drug discovery today.

[7]  Chi‐Hwa Wang,et al.  NANOPARTICLES OF BIODEGRADABLE POLYMERS FOR CANCER CHEMOTHARAPY , 2022 .

[8]  M. Rafiee-Tehrani,et al.  Transport of octreotide and evaluation of mechanism of opening the paracellular tight junctions using superporous hydrogel polymers in Caco-2 cell monolayers. , 2004, Journal of pharmaceutical sciences.

[9]  D. Boykin,et al.  Enhanced Permeability of the Antimicrobial Agent 2,5-Bis(4-Amidinophenyl)Furan Across Caco-2 Cell Monolayers Via Its Methylamidoxime Prodrug , 2002, Pharmaceutical Research.

[10]  G. Russell-Jones,et al.  Lectin-mediated transport of nanoparticles across Caco-2 and OK cells. , 1999, International journal of pharmaceutics.

[11]  Sven Frokjaer,et al.  In-depth evaluation of Gly-Sar transport parameters as a function of culture time in the Caco-2 cell model. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[12]  P. Swaan.  Recent Advances in Intestinal Macromolecular Drug Delivery via Receptor-Mediated Transport Pathways , 1998, Pharmaceutical Research.

[13]  I. Hidalgo,et al.  Assessing the absorption of new pharmaceuticals. , 2001, Current topics in medicinal chemistry.

[14]  J. Hochman,et al.  P-glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4. , 2001, The Journal of pharmacology and experimental therapeutics.

[15]  J. Beaulieu,et al.  Transient mosaic patterns of morphological and functional differentiation in the Caco-2 cell line. , 1992, Gastroenterology.

[16]  E. Biganzoli,et al.  Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics. , 1999, Farmaco.

[17]  Thomas J. Vidmar,et al.  The Madin Darby Canine Kidney (MDCK) Epithelial Cell Monolayer as a Model Cellular Transport Barrier , 2004, Pharmaceutical Research.

[18]  G. Pauletti,et al.  High glucose concentration in isotonic media alters Caco-2 cell permeability , 2008, AAPS PharmSci.

[19]  R. Conradi,et al.  Caco-2 Cell Monolayers as a Model for Drug Transport Across the Intestinal Mucosa , 1990, Pharmaceutical Research.

[20]  Gerrit Borchard,et al.  The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro , 1996 .

[21]  J. J. van de Sandt,et al.  Monolayers of IEC-18 cells as an in vitro model for screening the passive transcellular and paracellular transport across the intestinal barrier: comparison of active and passive transport with the human colon carcinoma Caco-2 cell line. , 2002, Environmental toxicology and pharmacology.

[22]  Leo Abrahamse,et al.  Comparison of in Vitro Models for the Prediction of Compound Absorption across the Human Intestinal Mucosa , 2004, Journal of biomolecular screening.

[23]  Y Zhang,et al.  Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. , 1998, Journal of pharmaceutical sciences.

[24]  P. Artursson,et al.  Transport of celiprolol across human intestinal epithelial (Caco‐2) cells: mediation of secretion by multiple transporters including P‐glycoprotein , 1993, British journal of pharmacology.

[25]  Peter W. Swaan,et al.  Microfabricated Porous Silicon Particles Enhance Paracellular Delivery of Insulin Across Intestinal Caco-2 Cell Monolayers , 2004, Pharmaceutical Research.

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

[27]  Risto Kostiainen,et al.  N-in-One Permeability Studies of Heterogeneous Sets of Compounds Across Caco-2 Cell Monolayers , 2003, Pharmaceutical Research.

[28]  J. Shao,et al.  Normal flora: living vehicles for non-invasive protein drug delivery. , 2004, International journal of pharmaceutics.

[29]  Lawrence X. Yu,et al.  In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. , 2004, Current opinion in drug discovery & development.

[30]  Richard A. Morrison,et al.  Evaluation of Biocoat® Intestinal Epithelium Differentiation Environment (3-Day Cultured Caco-2 Cells) as an Absorption Screening Model with Improved Productivity , 1997, Pharmaceutical Research.

[31]  J. Tolan,et al.  MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. , 1999, Journal of pharmaceutical sciences.

[32]  U. Christians,et al.  Active transport of the angiotensin‐II antagonist losartan and its main metabolite EXP 3174 across MDCK‐MDR1 and Caco‐2 cell monolayers , 2000, British journal of pharmacology.

[33]  P. Artursson,et al.  Co-cultures of human intestinal goblet (HT29-H) and absorptive (Caco-2) cells for studies of drug and peptide absorption , 1995 .

[34]  P. Nicklin,et al.  Transfer of metformin across monolayers of human intestinal Caco-2 cells and across rat intestine , 1996 .

[35]  T. Tsuruo,et al.  Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators. , 1993, The Journal of biological chemistry.

[36]  J. Fix.  Strategies for delivery of peptides utilizing absorption-enhancing agents. , 1996, Journal of pharmaceutical sciences.

[37]  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 .

[38]  Z. Değim,et al.  The effect of various liposome formulations on insulin penetration across Caco-2 cell monolayer. , 2004, Life sciences.

[39]  J. Leroux,et al.  Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles. , 2003, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[40]  M Rowland,et al.  Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia. , 2001, The Journal of pharmacology and experimental therapeutics.

[41]  G Mannens,et al.  Strategies for absorption screening in drug discovery and development. , 2001, Current topics in medicinal chemistry.

[42]  H. M. Nielsen,et al.  Drug delivery studies in Caco-2 monolayers. II. Absorption enhancer effects of lysophosphatidylcholines , 1995 .

[43]  S. Chong,et al.  Validation of the 96 well Caco-2 cell culture model for high throughput permeability assessment of discovery compounds. , 2005, International journal of pharmaceutics.

[44]  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.

[45]  D. Thakker,et al.  Enhancing paracellular permeability by modulating epithelial tight junctions. , 2000, Pharmaceutical science & technology today.

[46]  J. G. Eley,et al.  Evaluation of dodecylmaltoside as a permeability enhancer for insulin using human carcinoma cells. , 2005, Journal of pharmaceutical sciences.

[47]  W. Rubas,et al.  Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit, Monkey, and Dog Intestine and Human Drug Absorption , 2004, Pharmaceutical Research.

[48]  L. Lim,et al.  Uptake of Chitosan and Associated Insulin in Caco-2 Cell Monolayers: A Comparison Between Chitosan Molecules and Chitosan Nanoparticles , 2003, Pharmaceutical Research.

[49]  Z. Zuo,et al.  Evaluation of the first-pass glucuronidation of selected flavones in gut by Caco-2 monolayer model. , 2004, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[50]  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.

[51]  J. Beijnen,et al.  Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[52]  L. Bromberg,et al.  Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[53]  I. Hidalgo,et al.  Transport of a large neutral amino acid (phenylalanine) in a human intestinal epithelial cell line: Caco-2. , 1990, Biochimica et biophysica acta.

[54]  R. Ducroc,et al.  Horseradish peroxidase transport across adult rabbit jejunum in vitro. , 1982, The American journal of physiology.

[55]  M. Wirth,et al.  Binding and Uptake of Wheat Germ Agglutinin-Grafted PLGA-Nanospheres by Caco-2 Monolayers , 2004, Pharmaceutical Research.

[56]  A. Blais,et al.  Common characteristics for Na+-dependent sugar transport in Caco-2 cells and human fetal colon , 2005, The Journal of Membrane Biology.

[57]  Gordon L. Amidon,et al.  The Mechanism of Uptake of Biodegradable Microparticles in Caco-2 Cells Is Size Dependent , 1997, Pharmaceutical Research.

[58]  N. Schipper,et al.  Automated Absorption Assessment Using Caco-2 Cells Cultured on Both Sides of Polycarbonate Membranes , 1999, Pharmaceutical Research.

[59]  A. Waseem Malick,et al.  The use of the intestinal epithelial cell culture model, Caco-2, in pharmaceutical development , 1996 .

[60]  J. H. Kou,et al.  Effect of solubilizing excipients on permeation of poorly water-soluble compounds across Caco-2 cell monolayers. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[61]  Nicholas A Peppas,et al.  Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[62]  P. Watkins,et al.  Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3. , 1997, Molecular pharmacology.

[63]  Y. Zhu,et al.  Mechanisms and kinetics of uptake and efflux of L-methionine in an intestinal epithelial model (Caco-2). , 1994, The Journal of nutrition.

[64]  H. Junginger,et al.  Effects of various absorption enhancers on transport of clodronate through Caco-2 cells. , 2003, International journal of pharmaceutics.

[65]  I. Legen,et al.  Comparison of different intestinal epithelia as models for absorption enhancement studies. , 2005, International journal of pharmaceutics.

[66]  H. Junginger,et al.  Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2). , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[67]  J. Mönkkönen,et al.  Characterization of Caco-2 cell monolayer drug transport properties by cassette dosing using UV/fluorescence HPLC. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[68]  D. Thakker,et al.  USE OF CACO-2 CELLS AS AN IN VITRO INTESTINAL ABSORPTION AND METABOLISM MODEL , 1994 .

[69]  M. Wirth,et al.  Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[70]  J. Polli,et al.  Targeted drug delivery systems 6: Intracellular bioreductive activation, uptake and transport of an anticancer drug delivery system across intestinal Caco-2 cell monolayers. , 2001, International journal of pharmaceutics.

[71]  L. Illum,et al.  Chitosan and its use as a pharmaceutical excipient. , 1998, Pharmaceutical research.

[72]  Antony D'Emanuele,et al.  The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[73]  R. Conradi,et al.  In Vitro/in Vivo Models for Peptide Oral Absorption: Comparison of Caco-2 Cell Permeability with Rat Intestinal Absorption of Renin Inhibitory Peptides , 1993, Pharmaceutical Research.

[74]  R. Micetich,et al.  High-throughput caco-2 cell permeability screening by cassette dosing and sample pooling approaches using direct injection/on-line guard cartridge extraction/tandem mass spectrometry. , 2000, Rapid communications in mass spectrometry : RCM.

[75]  W. Lubitz,et al.  Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco-2 cells. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

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

[77]  M. Kataoka,et al.  Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[78]  Gérard Hopfgartner,et al.  P‐Glycoprotein and Surfactants: Effect on Intestinal Talinolol Absorption , 2005, Clinical pharmacology and therapeutics.

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

[80]  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.

[81]  S. Rossi,et al.  Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco‐2 cell lines, and rat jejunum , 2004, The Journal of pharmacy and pharmacology.

[82]  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 .

[83]  I. Hidalgo,et al.  Transport of bile acids in a human intestinal epithelial cell line, Caco-2. , 1990, Biochimica et biophysica acta.

[84]  P. Annaert,et al.  Drug absorption studies of prodrug esters using the Caco-2 model: evaluation of ester hydrolysis and transepithelial transport , 1998 .

[85]  K. Iseki,et al.  Development of a new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract. , 2001, International journal of pharmaceutics.

[86]  S. Yamashita,et al.  Characterization of Drug Transport Through Tight-Junctional Pathway in Caco-2 Monolayer: Comparison with Isolated Rat Jejunum and Colon , 1995, Pharmaceutical Research.

[87]  P. Artursson,et al.  Starch microspheres induce pulsatile delivery of drugs and peptides across the epithelial barrier by reversible separation of the tight junctions. , 1995, Journal of drug targeting.

[88]  M. A. Moseley,et al.  CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells. , 1996, Drug metabolism and disposition: the biological fate of chemicals.

[89]  P. Augustijns,et al.  Implementation of the caco-2 cell culture model as a predictive tool for the oral absorption of drugs. In-house evaluation procedures. , 2002, Journal de pharmacie de Belgique.

[90]  J. Weinstein,et al.  Interactions of liposomes with mammalian cells. , 1978, Annual review of biophysics and bioengineering.

[91]  S. Stavchansky,et al.  Link between drug absorption solubility and permeability measurements in Caco-2 cells. , 1998, Journal of pharmaceutical sciences.

[92]  R. Yumoto,et al.  Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. , 1998, European journal of pharmacology.

[93]  F. Merkus,et al.  Effects of Absorption Enhancers on Rat Nasal Epithelium in Vivo: Release of Marker Compounds in the Nasal Cavity , 1995, Pharmaceutical Research.

[94]  P. Artursson.  Cell cultures as models for drug absorption across the intestinal mucosa. , 1991, Critical reviews in therapeutic drug carrier systems.

[95]  Lasse Murtomäki,et al.  Drug permeation in biomembranes: in vitro and in silico prediction and influence of physicochemical properties. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[96]  J. Cogburn,et al.  A Model of Human Small Intestinal Absorptive Cells. 1. Transport Barrier , 1991, Pharmaceutical Research.

[97]  J. Groten,et al.  Comparison of permeability characteristics of the human colonic Caco-2 and rat small intestinal IEC-18 cell lines , 1997 .

[98]  J. Polli,et al.  Prediction of dissolution-absorption relationships from a dissolution/Caco-2 system. , 1999, International journal of pharmaceutics.

[99]  C. Shim,et al.  Preparation and evaluation of proliposomes containing salmon calcitonin. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[100]  J. Shao,et al.  Transepithelial Electrical Resistance is Not a Reliable Measurement of the Caco-2 Monolayer Integrity in Transwell , 2004, Drug delivery.

[101]  K. Bock,et al.  Serotonin glucuronidation by Ah receptor- and oxidative stress-inducible human UDP-glucuronosyltransferase (UGT) 1A6 in Caco-2 cells. , 2005, Biochemical pharmacology.

[102]  J. Crison,et al.  A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability , 1995, Pharmaceutical Research.

[103]  C. Shim,et al.  Characterization of the Transport of Uracil Across Caco-2 and LLC-PK1 Cell Monolayers , 2002, Pharmaceutical Research.

[104]  J. R. Sportsman,et al.  Association of intestinal peptide transport with a protein related to the cadherin superfamily. , 1994, Science.

[105]  K R Scott,et al.  Enhancing the permeation of marker compounds and enaminone anticonvulsants across Caco-2 monolayers by modulating tight junctions using zonula occludens toxin. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[106]  Ronald T Borchardt,et al.  A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. , 2002, Journal of pharmaceutical sciences.

[107]  S. Chong,et al.  Utility of 96 well Caco-2 cell system for increased throughput of P-gp screening in drug discovery. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[108]  J. Beijnen,et al.  P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. , 2001, Molecular pharmacology.

[109]  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.

[110]  I. Kwon,et al.  Self-assembled “nanocubicle” as a carrier for peroral insulin delivery , 2002, Diabetologia.

[111]  H. Brøndsted,et al.  Drug Delivery Studies in Caco-2 Monolayers. Synthesis, Hydrolysis, and Transport of O-Cyclopropane Carboxylic Acid Ester Prodrugs of Various β-Blocking Agents , 1995, Pharmaceutical Research.

[112]  P. Daddona,et al.  Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin. , 1998, Journal of pharmaceutical sciences.

[113]  Claude Roques,et al.  Correlation Between Oral Drug Absorption in Humans, and Apparent Drug Permeability in TC-7 Cells, A Human Epithelial Intestinal Cell Line: Comparison with the Parental Caco-2 Cell Line , 1998, Pharmaceutical Research.

[114]  B. Lacour,et al.  Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates , 1999, British journal of pharmacology.

[115]  James E Polli,et al.  Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[116]  A. Dantzig,et al.  Uptake of the cephalosporin, cephalexin, by a dipeptide transport carrier in the human intestinal cell line, Caco-2. , 1990, Biochimica et biophysica acta.

[117]  P. Augustijns,et al.  Use of Caco-2 cells and LC/MS/MS to screen a peptide combinatorial library for permeable structures. , 1999, International journal of pharmaceutics.

[118]  Y. Berger,et al.  The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications , 1995, Cell Biology and Toxicology.

[119]  P. Artursson,et al.  A conditionally immortalized epithelial cell line for studies of intestinal drug transport. , 1999, The Journal of pharmacology and experimental therapeutics.

[120]  R. D. de Water,et al.  Cytotoxic effects of pamidronate on monolayers of human intestinal epithelial (Caco-2) cells and its epithelial transport. , 1994, Journal of pharmaceutical sciences.

[121]  H. M. Nielsen,et al.  Drug delivery studies in Caco-2 monolayers. III. Intestinal transport of various vasopressin analogues in the presence of lysophosphatidylcholine , 1995 .

[122]  Ming Hu,et al.  Mechanism of L-α-Methyldopa Transport Through a Monolayer of Polarized Human Intestinal Epithelial Cells (Caco-2) , 1990, Pharmaceutical Research.

[123]  F. Merkus,et al.  Absorption enhancers in nasal drug delivery: efficacy and safety , 1993 .

[124]  N. Peppas,et al.  Investigation of the cytotoxicity and insulin transport of acrylic-based copolymer protein delivery systems in contact with Caco-2 cultures. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[125]  J. Alsenz,et al.  Development of a 7-Day, 96-Well Caco-2 Permeability Assay with High-Throughput Direct UV Compound Analysis , 2003, Pharmaceutical Research.

[126]  H. Junginger,et al.  N-Trimethyl Chitosan Chloride as a Potential Absorption Enhancer Across Mucosal Surfaces: In Vitro Evaluation in Intestinal Epithelial Cells (Caco-2) , 1997, Pharmaceutical Research.