title: Reduced ABCB1 Expression and Activity in the Presence of Acrylic Copolymers.
abstract: OBJECTIVE
  P-glycoprotein (P-gp; ABCB1), an integral membrane protein in the apical surface of human intestinal epithelial cells, plays a crucial role in the intestinal transport and efflux leading to changes in the bioavailability of oral pharmaceutical compounds. This study was set to examine the potential effects of three Eudragits RL100, S100 and L100 on the intestinal epithelial membrane transport of rhodammine-123 (Rho-123), a substrate of P-gp using a monolayer of human colon cancer cell line (Caco-2).
  
  
  METHODS
  The least non-cytotoxic concentrations of the excipients were assessed in Caco-2 cells by the MTT assay. Then the transepithelial transport of Rho-123 across Caco-2 monolayers was determined with a fluorescence spectrophotometer. Besides, the expression of the P-gp in cells exposed to the polymers was demonstrated using Western-blotting analysis.
  
  
  RESULTS
  Treatment of cells with Eudragit RL100 and L100 led to a very slight change while Eudragit S100 showed 61% increase in Rho-123 accumulation (P<0.001) and also reduced transporter expression.
  
  
  CONCLUSIONS
  Our studies suggest that using proper concentrations of the Eudragit S100 in drug formulation would improve intestinal permeability and absorption of p-gp substrate drugs.
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Mohammadzadeh
authors.affiliation: Immunology Research Center and School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
authors.affiliation: Immunology Research Center and School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Yousefi
authors.affiliation: Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
keywords: ABCB1; Eudragit; Intestinal efflux pump; P-glycoprotein; Rhodamine
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