Use of CACO-2 Cells as an in vitro Intestinal Absorption and Metabolism Model

Gan, Liang Shang; Eads, Cindy A.; Niederer, T.; Bridgers, Avis; Yanni, Souzan B.; Hsyu, Poe‐Hirr; Pritchard, Fred J.; Thakker, Dhiren R.

doi:10.3109/03639049409038322

Cited by 31 publications

(9 citation statements)

References 16 publications

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“…We synthesized a selection of compounds from Library 1 and evaluated their cell permeabilities in Caco-2 cells . We chose eight compounds (Figure A) with diverse functional side chains, MW, and ALogP values, which were all successfully synthesized by the same method used for library synthesis and purified by reverse-phase column chromatography.…”

Section: Resultsmentioning

confidence: 72%

Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry

et al. 2016

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Synthetic and natural cyclic peptides provide a testing ground for studying membrane permeability in nontraditional drug scaffolds. Cyclic peptomers, which incorporate peptide and N-alkylglycine (peptoid) residues, combine the stereochemical and geometric complexity of peptides with the functional group diversity accessible to peptoids. We synthesized cyclic peptomer libraries by split-pool techniques, separately permuting side chain and backbone geometry, and analyzed their membrane permeabilities using the parallel artificial membrane permeability assay. Nearly half of the side chain permutations had permeability coefficients (P) > 1 × 10 cm/s. Some backbone geometries enhanced permeability due to their ability to form more stable intramolecular hydrogen bond networks compared with other scaffolds. These observations suggest that hexameric cyclic peptomers can have good passive permeability even in the context of extensive side chain and backbone variation, and that high permeability can generally be achieved within a relatively wide lipophilicity range.

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Section: Resultsmentioning

confidence: 72%

Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry

et al. 2016

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“…Two families of transporters, multidrug resistance (MDR) and multidrug resistance-associated protein (MRP) (27)(28)(29), mediate apical drug efflux. P-Glycoprotein (P-gp), the product of the MDR1 gene, is the most studied member of the apical efflux transporters (30)(31)(32)(33)(34)(35) and has been shown to limit intestinal absorption of a large number of drugs (36)(37)(38)(39)(40)(41). Certain highly potent macromolecular drugs are transported via vesicular transport ( Figure 1).…”

Section: Drug Absorption Across the Intestinal Epitheliummentioning

confidence: 99%

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

Shah¹,

Jogani²,

Bagchi³

et al. 2006

Biotechnol. Prog.

204

125

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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.

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“…Therefore, in this study we investigated the effects of three free N‐PCPs and their respective complexes with calcium on the viability and on [Ca 2+ ] i of cultured Caco‐2 cells, a human adenocarcinoma cell line, which is a good model for intestinal epithelium (18‐22) . Besides alendronate and pamidronate, we tested for comparison olpadronate, a N‐PCP resembling structurally these two aminobisphosphonates (Fig.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Nitrogen-Containing Bisphosphonates on Human Epithelial (Caco-2) Cells, an In Vitro Model for Intestinal Epithelium

Twiss

Pas

Ramp‐Koopmanschap

et al. 1999

Journal of Bone and Mineral Research

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Nitrogen-containing bisphosphonates (N-PCP) are bisphosphonates with an increased antiresorptive potency. Aminobisphosphonates, N-PCPs with an amino group, can cause nonspecific gastrointestinal complaints. It is not known whether these side effects are specific for these bisphosphonates or for the whole class of N-PCPs. In this study, we investigated the effects of two aminobisphosphonates (pamidronate and alendronate) and a structurally similar N-PCP (olpadronate) and their three respective calcium complexes on the viability and the intracellular calcium concentration ([Ca 2+ ] i ) of cultured Caco-2 cells a model for intestinal epithelium. These cells were also examined for apoptosis or necrosis. In the presence of calcium, pamidronate and alendronate were toxic to the cells, with pamidronate being more toxic than alendronate. Olpadronate induced toxicity only at concentrations more than ten times higher than the toxic concentrations of pamidronate. In the absence of calcium definite signs of toxicity were observed only with pamidronate at clinically relevant concentrations. The complexes of pamidronate and alendronate with calcium were considerably less soluble than the olpadronate calcium complex. There were no signs of apoptosis. [Ca 2+ ] i was transiently raised after treatment with the N-PCPs. Doses at which responses were seen were, respectively, 0.02 mM (pamidronate), 0.3 mM (alendronate), and 2 mM (olpadronate). The peak of response was slightly greater after pamidronate treatment than after alendronate or olpadronate, respectively. In conclusion pamidronate, either as an ion or as a calcium complex, is the most toxic of the bisphosphonates tested for Caco-2 cells. Alendronate was less toxic while olpadronate was the least toxic in presence of calcium. The solubility of the bisphosphonate complexes with calcium may account for these differences in toxicity. (J Bone Miner Res 1999;14:784-791)

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Use of CACO-2 Cells as an in vitro Intestinal Absorption and Metabolism Model

Cited by 31 publications

References 16 publications

Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry

Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry

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

The Effects of Nitrogen-Containing Bisphosphonates on Human Epithelial (Caco-2) Cells, an In Vitro Model for Intestinal Epithelium

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