Bahman YOUSEFI, Hadi VALIZADEH, Parvin ZAKERI MILANI, Ramin MOHAMMADZADEH, Behzad BARADARAN

Attenuation of intestinal efflux pump thru polymers and preservatives

P-glycoprotein (P-gp), the efflux membrane protein found in the upper exterior of epithelial cells in human intestine, is capable of exhibiting variations in the intestinal transport. This study was set with the purpose of testing the capability often pharmaceutical excipients namely Carbopol, Xanthan, Tragacanth, Sodium Benzoate, Hydroxypropyl methylcellulose, Methylparaben, Methylcellulose, Cetyltrimethylammonium bromide and Vitamin E in regulating P-gp protein expression and the multidrug resistance (MDR1) gene, by means of a monolayer of human colon cancer cell line (Caco-2). Using MTT test, the least sub-toxic concentrations of mentioned excipients were assessed in Caco-2 cells. Subsequently the impact of the excipients on P-gp activity was evaluated by quantifying the amount of Rhodamine-123 uptake into cells. Besides, P-glycoprotein expression was scrutinized via Western-blotting. Among the tested excipients, Tragacanth and Xanthan showed a similar western blotting and Rhodamine-123 assay results as the control group. Carbopol 934, Vitamin E, and Methylcellulose showed 27.2%, 43% and 50.9% increase in Rhodamine accumulation, respectively. According to the obtained results it is concluded that using appropriate concentrations of the Carbopol 934, Vitamin E and Methylcellulose can attenuate the P-gp activity and expression where such reduction ought to be taken into consideration due to its role in the changes of permeability and absorption of the pharmaceutical compounds.

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