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Advanced Pharmaceutical Bulletin
ISSN: 2228-5881      eISSN: 2251-7308  
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Article History
Submitted: 21 Dec 2013
Revised: 04 Jan 2014
First published online: 07 Feb 2014

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Adv Pharm Bull. 2014;4(3):219-224 doi: 10.5681/apb.2014.032
PMID:24754004        PMCID:PMC3992956

Reduced ABCB1 Expression and Activity in the Presence of Acrylic Copolymers 

Original Research

Ramin Mohammadzadeh 1,2, Behzad Baradaran 3, Hadi Valizadeh 1, Bahman Yousefi 3, Parvin Zakeri-Milani 4 *

1 Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Immunology Research Center and School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.



Abstract
Purpose: 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.Conclusion: 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.





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