The Caco-2 cell monolayer is currently being considered a useful model for studying Fe uptake by human intestinal cells. In fact, an experimental protocol that conjugates the simulation techniques of the gastrointestinal digestion with the Fe internalizing phase by the Caco-2 cells has been set up. Such a protocol appears very useful and predictive of the in vivo behaviour so far as it takes into account the phase of Fe3+ dissolution in the gastro intestine and the subsequent permeation across the epithelium. Indeed it cannot be taken for granted that the latter phase is slower than the former and hence that it is the rate- determining one. It is known that at pH values higher than 3 the Fe3+ ion tends to form Fe(OH)3, the water solubility of which is practically null. For this reason the organism has developed an efficient transport system. Quite hypothetically another type of Fe3+ transport across the intestinal epithelium could involve the cellular endocytosis of a Fe3+ carrier (sucrosome, e.g., nano- or micro-particulate). For these reasons the Caco-2 cells model might not predict the in vivo bioavailability of Fe3+ which could reach the general circulation by internalization and subsequent release from the intestinal epithelial cells of the nano or micro-particulate Fe3+ carrier. Therefore, to evaluate the ability of the carrier to transport Fe3+ across the epithelium an ex vivo model based on excised rat intestine could be more predictive. The present work compares the two models, namely that based on the Caco-2 cells monolayer and that based on the excised rat intestine, for their ability to predict the absorption of Sucrosomial® Iron from different formulations supplied by Pharmanutra SpA. For Caco-2 cells absorption studies, Caco-2 cells were seeded in well plates, maintained in cell culture medium and used in the Fe uptake experiments at 14 days post- seeding. An aliquot of the intestinal digest was pipetted into the upper chamber and after 24 h-incubation, cells were harvested for analysis. For permeation studies, the intestinal mucosa was excised from non-fasting male Wistar rats. The excised intestine was cut into strips and mounted in Ussing-type chambers without stripping off the underlying muscle layer. Data described in this work has shown that the Sucrosomial® Iron formulations have the ability to promote the Fe3+ absorption across the intestinal epithelia, probably thanks to the endocytosis of the microparticulate Fe3+ carrier.

Sucrosomial iron and traditional iron dosage forms are compared for absorption by Caco2 cells

CARPI, SARA;
2016-01-01

Abstract

The Caco-2 cell monolayer is currently being considered a useful model for studying Fe uptake by human intestinal cells. In fact, an experimental protocol that conjugates the simulation techniques of the gastrointestinal digestion with the Fe internalizing phase by the Caco-2 cells has been set up. Such a protocol appears very useful and predictive of the in vivo behaviour so far as it takes into account the phase of Fe3+ dissolution in the gastro intestine and the subsequent permeation across the epithelium. Indeed it cannot be taken for granted that the latter phase is slower than the former and hence that it is the rate- determining one. It is known that at pH values higher than 3 the Fe3+ ion tends to form Fe(OH)3, the water solubility of which is practically null. For this reason the organism has developed an efficient transport system. Quite hypothetically another type of Fe3+ transport across the intestinal epithelium could involve the cellular endocytosis of a Fe3+ carrier (sucrosome, e.g., nano- or micro-particulate). For these reasons the Caco-2 cells model might not predict the in vivo bioavailability of Fe3+ which could reach the general circulation by internalization and subsequent release from the intestinal epithelial cells of the nano or micro-particulate Fe3+ carrier. Therefore, to evaluate the ability of the carrier to transport Fe3+ across the epithelium an ex vivo model based on excised rat intestine could be more predictive. The present work compares the two models, namely that based on the Caco-2 cells monolayer and that based on the excised rat intestine, for their ability to predict the absorption of Sucrosomial® Iron from different formulations supplied by Pharmanutra SpA. For Caco-2 cells absorption studies, Caco-2 cells were seeded in well plates, maintained in cell culture medium and used in the Fe uptake experiments at 14 days post- seeding. An aliquot of the intestinal digest was pipetted into the upper chamber and after 24 h-incubation, cells were harvested for analysis. For permeation studies, the intestinal mucosa was excised from non-fasting male Wistar rats. The excised intestine was cut into strips and mounted in Ussing-type chambers without stripping off the underlying muscle layer. Data described in this work has shown that the Sucrosomial® Iron formulations have the ability to promote the Fe3+ absorption across the intestinal epithelia, probably thanks to the endocytosis of the microparticulate Fe3+ carrier.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/87688
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