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We studied the toxic effects of amphotericin B and gramicidin S, alone and in combination, using free and liposome-encapsulated drugs. In vitro toxic effects of the drugs on human erythrocytes and Candida albicans were determined by measuring leakage of intracellular potassium ions (K+). Liposomal formulations of both drugs greatly reduced K+ leakage from human erythrocytes, whereas liposomal gramicidin S, but not liposomal amphotericin B, prevented K+ leakage from C. albicans. In both free and liposomal forms, the combinations of drugs produced decreased toxicity to erythrocytes compared with the drugs alone. This protective effect was more apparent with liposomal combinations than with free drug combinations. A significant increase in fungal cell toxicity was observed, however, when free and liposomal drug combinations were tested against C. albicans. The results suggest that optimal concentrations of liposomal drug combinations (amphotericin B and gramicidin S) may provide increased toxicity against fungal cells and simultaneously protect mammalian cells.

antimicrobial agents and chemotherapy

Effects of free and liposomal amphotericin B and gramicidin S alone and in combination on potassium leakage from human erythrocytes and Candida albicans