Article

Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa.

Kalamazoo College, Michigan Center, Michigan, United States
Pharmaceutical Research (Impact Factor: 3.95). 10/1990; 7(9):902-10. DOI: 10.1023/A:1015937605100
Source: PubMed

ABSTRACT Human colon adenocarcinoma (Caco-2) cells, when grown on semipermeable filters, spontaneously differentiate in culture to form confluent monolayers which both structurally and functionally resemble the small intestinal epithelium. Because of this property they show promise as a simple, in vitro model for the study of drug absorption and metabolism during absorption in the intestinal mucosa. In the present study, the transport of several model solutes across Caco-2 cell monolayers grown in the Transwell diffusion cell system was examined. Maximum transport rates were found for the actively transported substance glucose and the lipophilic solutes testosterone and salicyclic acid. Slower rates were observed for urea, hippurate, and saliylate anions and were correlated with the apparent partition coefficient of the solute. These results are similar to what is found with the same compounds in other, in vivo absorption model systems. It is concluded that the Caco-2 cell system may give useful predictions concerning the oral absorption potential of new drug substances.

1 Bookmark
 · 
133 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cocoa butter (CB) is a largely used excipient in pharmaceutical field. Aim of this work was to set formulative parameters for the preparation of SLN based on “green” lipid matrix for drug delivery as natural, both human and environmental safe systems. Double emulsion technique (w1/o/w2) was selected for SLN preparation. The effect on the dimensional properties of different surfactants (Tween 80 and PEG 40 monostearate) and co-surfactants (PEG400 monostearate, Emulium® Kappa2 and Plurol®Stearique) at different concentrations was evaluated. Stability tests were performed. SLN dispersions were exsiccated and the effect of the dried process on SLN size was evaluated. The influence of temperature on SLN dimensions was investigated at 37 °C. MTT test was performed on raw materials and formulations. The w1/o/w2 is suitable, rapid and economic technique for the preparation of CB SLN. Tween 80-Plurol Stearique combination gives the best results: particles size less than 400 nm and PI of about 0.4 are obtained when PS 2% is used. Both raw materials and formulations are safe. The importance to evaluate the effect of different surfactant and/or co-surfactant on the dimensional properties of SLN is evident by selecting substances with preferable safety profiles, and favorable environmental properties to develop stable “green” SLN.
    Pharmaceutical Development and Technology 10/2014; DOI:10.3109/10837450.2014.971376 · 1.33 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: To date, the Caco-2 model is considered as the gold standard to predict intestinal drug absorption. Often, aqueous phosphate buffers are used as apical medium. The purpose of this study was to use fasted state human intestinal fluid (FaHIF) as apical solvent system to generate biorelevant permeability values for a series of 16 model drugs that can be used as reference data to critically evaluate fasted state simulated intestinal fluid (FaSSIF) as possible substitute medium. Caco-2 compatibility with FaHIF was achieved when 50mg/ml mucus was applied on top of the cells before adding the apical medium. The use of FaHIF as solvent system generated a broad range of apparent permeability values (Papp) for the series of model compounds. When Papp values obtained with FaHIF were compared to those obtained with FaSSIF, a strong correlation was observed (R=0.951). The use of FaSSIF in the absence of mucus did not significantly alter this correlation. For FaHIF, FaSSIF and reference phosphate buffer blank FaSSIF, a strong sigmoidal relationship was found between Papp and fahuman, illustrated by correlation coefficients of 0.961, 0.893 and 0.868, respectively. In terms of inter-subject variability, the use of FaHIF from different volunteers originating from two distinct age groups (18-25years; 65-72years) exhibited an average coefficient of variance (CV) of 30%. However, no age dependency in permeability could be observed. In conclusion, the data generated in this article justify the use of FaSSIF as biorelevant apical medium in the Caco-2 assay to accurately predict in vivo drug absorption. Also, the optimized mucus-containing Caco-2 model can be used in combination with intestinal fluid samples aspirated after drug administration to further investigate intraluminal drug and formulation behavior. Copyright © 2014 Elsevier B.V. All rights reserved.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 01/2015; 67:126-35. DOI:10.1016/j.ejps.2014.11.010 · 2.61 Impact Factor