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

Abstract

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.

Direct surfactin–gramicidin S antagonism supports detoxification in mixed producer cultures of Bacillus subtilis and Aneurinibacillus migulanus

“…GS primarily acts as a defence molecule, but also retards the sporulation of its producer (Azuma & Demain, 1996;Nandi & Seddon, 1978). Both the anionic Srf and cationic GS have membranolytic activity (Maget-Dana & Ptak, 1995;Epand & Vogel, 1999) and are active against Gram-positive bacteria (Tsukagoshi et al, 1970; Kondejewski et al, 1996), as well as fungi (Midez et al, 1989;Tsukagoshi et al, 1970). However, Srf is generally less active than GS (this study), but possesses comparable haemolytic activity (Kracht et al, 1999;Katsu et al, 1988).…”

Amphotericin B susceptibility testing of Candida species by flow cytometry

“…following 60 min exposure to lethal concentrations of the drug (6). We found that 3 h r exposure to 2.5 pg AmpBiml was necessary in order to maximize ETBR fluorescence of the cells (Fig 2).…”

A method for the facile solid-phase synthesis of gramicidin S and its analogs

“…1). Gramicidin S exhibits many clinically interesting features, including strong antibacterial and antifungal activity [1,2], broad immuno-suppressive properties [3], antitumor activity [4], DNA transfective properties [5] and protease inhibitor activities [6]. Since its discovery in the 1940s, more than 200 analogs of gramicidin S have been prepared and characterized chemically, physically *To whom correspondence should be addressed.…”