Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2484662 | Journal of Pharmaceutical Sciences | 2014 | 13 Pages |
Abstract
Sucrose fatty acid esters are increasingly used as excipients in pharmaceutical products, but few data are available on their toxicity profile, mode of action, and efficacy on intestinal epithelial models. Three waterâsoluble sucrose esters, palmitate (Pâ1695), myristate (Mâ1695), laurate (Dâ1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40, were tested on Cacoâ2 cells. Cacoâ2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins claudinâ1, ZOâ1, and βâcatenin. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability for atenolol, fluorescein, vinblastine, and rhodamine 123 in Cacoâ2 monolayers. No visible opening of the tight junctions was induced by sucrose esters assessed by immunohistochemistry and electron microscopy, but some alterations were seen in the structure of filamentous actin microfilaments. Sucrose esters fluidized the plasma membrane and enhanced the accumulation of efflux transporter ligands rhodamine 123 and calcein AM in epithelial cells, but did not inhibit the Pâglycoprotein (Pâgp)âmediated calcein AM accumulation in MESâSA/Dx5 cell line. These data indicate that in addition to their dissolutionâincreasing properties sucrose esters can enhance drug permeability through both the transcellular and paracellular routes without inhibiting Pâgp. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3107-3119, 2014
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Lóránd Kiss, Ãva Hellinger, AnaâMaria Pilbat, Ágnes Kittel, Zsolt Török, András Füredi, Gergely Szakács, Szilvia Veszelka, Péter Sipos, Béla Ãzsvári, László G. Puskás, Monika Vastag, Piroska SzabóâRévész, Mária A. Deli,