Sucrose esters increase drug penetration, but do not inhibit P-glycoprotein in Caco-2 intestinal epithelial cells

Lóránd Kiss, Éva Hellinger, Ana Maria Pilbat, Ágnes Kittel, Zsolt Tö Rök, Furedi, Gergely Szakács, Szilvia Veszelka, Péter Sipos, B. Éla Ózsvári, László G. Puskás, Monika Vastag, Piroska Szabó -RÉVÉSZ, Mária A. Deli

Research output: Article

23 Citations (Scopus)

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 water-soluble sucrose esters, palmitate (P-1695), myristate (M-1695), laurate (D-1216), and two reference absorption enhancers, Tween 80 and Cremophor RH40, were tested on Caco-2 cells. Caco-2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins claudin-1, ZO-1, and β-catenin. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability for atenolol, fluorescein, vinblastine, and rhodamine 123 in Caco-2 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 P-glycoprotein (P-gp)-mediated calcein AM accumulation in MES-SA/Dx5 cell line. These data indicate that in addition to their dissolution-increasing properties sucrose esters can enhance drug permeability through both the transcellular and paracellular routes without inhibiting P-gp.

Original languageEnglish
Pages (from-to)3107-3119
Number of pages13
JournalJournal of pharmaceutical sciences
Volume103
Issue number10
DOIs
Publication statusPublished - okt. 12 2014

ASJC Scopus subject areas

  • Pharmaceutical Science

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