Caco‐2 Cells as a Model for Intestinal Absorption

Angelis, De; Turco, Laura

doi:10.1002/0471140856.tx2006s47

Cited by 107 publications

(85 citation statements)

References 22 publications

(22 reference statements)

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“…TEER determination is a simple and rapid technique that gives information about the integrity of the epithelial tight junctions and cell monolayers (Angelis & Turco, ). TEER values of the epithelial monolayer would greatly decreased resulting from the transport of ions via the paracellular route as the tight junction opens.…”

Section: Resultsmentioning

confidence: 99%

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Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for enhancing the cellular uptake of fish-derived peptide

Zhao

et al. 2018

J Food Biochem

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Methodology to enhance the intestinal absorption of peptides is an important challenge due to their easily degradation and poor permeability across the intestinal epithelium. In this study, the fish‐derived peptide (DGDDGEAGKIG)‐loaded chitosan (CS) nanoparticles (CS/PEP‐NPs) were prepared and investigated in Caco‐2 monolayer model. The results indicated zeta potential of CS/PEP‐NPs increased with the increase in molecular weight of CS (10–50 kDa). Transmission electron microscopy images revealed the CS/PEP‐NPs were uniform spherical‐shaped nanoparticles with a diameter of 50–200 nm (150 kDa). Compared to other CS/PEP‐NPs, 150‐kDa CS/PEP‐NPs performed an outstanding apparent permeability coefficient (Papp, 2.29 × 10−5 cm s−1) and cumulative amount of peptide (120 min, 2,987 ng) in Caco‐2 cells. CS/PEP‐NPs could reduce the tight junction integrity of Caco‐2 cells and enhance the intracellular fluorescence intensities of fluorescein isothiocyanate‐labeled peptide. These findings suggest that chitosan nanoparticles are promising carriers to promote intestinal absorption of fish‐derived peptide via paracellular pathway mediated by tight junctions. Practical applications Chitosans are promising carriers to promote intestinal absorption of fish‐derived peptide. The 150‐kDa CS/PEP‐NPs performed an outstanding apparent permeability coefficient (Papp, 2.29 × 10−5 cm s−1) and cumulative amount of peptide (120 min, 2,987 ng) in Caco‐2 cells. CS/PEP‐NPs could reduce the tight junction integrity of Caco‐2 cells and enhance the peptide uptake by paracellular pathway. Chitosan nanoparticles can be developed as vehicles for enhancing the cellular uptake of peptide in food industry.

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Section: Resultsmentioning

confidence: 99%

“…TEER determination is a simple and rapid technique that gives information about the integrity of the epithelial tight junctions and cell monolayers (Angelis & Turco, 2011).…”

Section: Apparent Permeability and Cumulative Amount Of Peptide Tramentioning

confidence: 99%

Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for enhancing the cellular uptake of fish-derived peptide

Zhao

et al. 2018

J Food Biochem

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“…The relative stability of CEE at gastric pH provides a rationale for potentially enhancing GI absorption of CEE by administration with food to delay gastric emptying, thereby promoting gastric absorption of intact CEE and slowing delivery of CEE to the higher pH environment of the small intestine where it would be less stable. While GI absorption for CEE has not been established in vivo, permeability studies conducted in Caco-2 monolayers, a commonly used cell culture model for intestinal absorption (Angelis & Turco, 2011), demonstrate that CEE is considerably more permeable than either CRT monohydrate or CRN (Table 2). …”

Section: Resultsmentioning

confidence: 99%

pH-Dependent Stability of Creatine Ethyl Ester: Relevance to Oral Absorption

Gufford

Ezell

Robinson

et al. 2013

Journal of Dietary Supplements

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Creatine ethyl ester hydrochloride (CEE) was synthesized as a prodrug of creatine (CRT) to improve aqueous solubility, gastrointestinal permeability, and ultimately the pharmacodynamics of CRT. We used high-performance liquid chromatography (HPLC) and proton nuclear magnetic resonance (NMR) to characterize the pH-dependent stability of CEE in aqueous solution and compared the permeability of CEE to CRT and creatinine (CRN) across Caco-2 human epithelial cell monolayers and transdermal permeability across porcine skin. CEE was most stable in a strongly acidic condition (half-life = 570 hours at pH 1.0) where it undergoes ester hydrolysis to CRT and ethanol. At pH ≥ 1.0, CEE cyclizes to CRN with the logarithm of the first order rate constant increasing linearly with pH. Above pH 8.0 (half-life = 23 sec) the rate of degradation was too rapid to be determined. The rate of degradation of CEE in cell culture media and simulated intestinal fluid (SIF) was a function of pH and correlated well with the stability in aqueous buffered solutions. The permeability of CEE across Caco-2 monolayers and porcine skin was significantly greater than that of CRT or CRN. The stability of CEE in acidic media together with its improved permeability suggests that CEE has potential for improved oral absorption compared to CRT.

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“…However, its applicability is extremely restricted due to its complexity, high cost, and ethical considerations. Several in vitro and in situ methods were developed for the measurement of permeability, including the parallel artificial membrane permeability assay, [24][25][26][27] everted gut sacs, [28][29][30] Ussing side-by-side diffusion chambers, 12,[31][32][33][34] Caco-2 monolayers, [35][36][37] and intestinal perfusion models for example, the rat single-pass intestinal perfusion (SPIP), [38][39][40][41] and the Doluisio technique. 37,[42][43][44] These methods are now well established and frequently used; yet, to assess segmental-dependent intestinal absorption throughout the GIT, rat intestinal perfusion still remain the most significant experimental method.…”

Section: Introductionmentioning

confidence: 99%

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

Wolk

Marković

Porat

et al. 2019

Journal of Pharmaceutical Sciences

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The goal of this work was to develop an in silico model that allows predicting segmental-dependent permeability throughout the small intestine (SI). In vivo permeability of 11 model drugs in 3 SI segments (jejunum, mid-SI, ileum) was studied in rats, creating a data set that reflects the conditions throughout the SI. Then, a predictive model was developed, combining physicochemical drug properties influencing the underlying mechanism of passive permeability: Log p, polar surface area, M, H-bond count, and Log f, with microenvironmental SI conditions. Excellent correlation was evident between the predicted and experimental data (R = 0.914), with similar predictability in each SI segment. Log p and Log f were identified as the major determinants of permeability, with similar contribution. Total H-bond count was also a significant determinant, followed by polar surface area and M. Leaving out any of the model parameters decreased its predictability. The model was validated against 5 external drugs, with excellent predictability. Notably, the model was able to predict the segmental-dependent permeability of all drugs showing this trend experimentally. Model predictability was better in the high-permeability versus low-permeability range. Overall, our approach of constructing a straightforward in silico model allowed reliable predictions of segmental-dependent intestinal permeability, providing new insights into relative effects of drug-related factors and gastrointestinal environment on permeability.

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Caco‐2 Cells as a Model for Intestinal Absorption

Cited by 107 publications

References 22 publications

Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for enhancing the cellular uptake of fish-derived peptide

Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for enhancing the cellular uptake of fish-derived peptide

pH-Dependent Stability of Creatine Ethyl Ester: Relevance to Oral Absorption

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

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