Modulation of the polyene antibiotic amphotericin B selective toxicity by pH change of the stock solutions


Belkherroubi-Sari L1, Boucherit Z1, Chéron M2, Boucherit K1, Benyoucef M1 andBelbraouet S3

Stock solutions of the polyene antibiotic amphotericin B (AmB) were prepared at pHs from 4.0 to 5.4 in acetic acid/acetate buffer, at 7.4 in phosphate-buffered saline (PBS), and from 10.0 to 10.8 in carbonate/bicarbonate buffer. Their antifungal activity was tested on Candida albicans cells and their toxicity on human erythrocytes. Antifungal activity was observed for all preparations. Surprisingly, the toxicity (K+ release and hemolysis) drastically decreased for the two preparations at pH 5.4 and 10.8. This effect was attributed, in the first case, to a screening of the positively charged aggregated antibiotic by the negatively charged acetate ions of the buffer, and, in the second case, to a neat modification of the mode of AmB self-association.

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