Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Feb;33(2):152–155. doi: 10.1128/aac.33.2.152

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

J A Midez 1, R L Hopfer 1, G Lopez-Berestein 1, R T Mehta 1
PMCID: PMC171447  PMID: 2470332

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.

Full text

PDF
152

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brajtburg J., Kobayashi D., Medoff G., Kobayashi G. S. Antifungal action of amphotericin B in combination with other polyene or imidazole antibiotics. J Infect Dis. 1982 Aug;146(2):138–146. doi: 10.1093/infdis/146.2.138. [DOI] [PubMed] [Google Scholar]
  2. Gale E. F. The release of potassium ions from Candida albicans in the presence of polyene antibiotics. J Gen Microbiol. 1974 Feb;80(2):451–465. doi: 10.1099/00221287-80-2-451. [DOI] [PubMed] [Google Scholar]
  3. Georgopapadakou N. H., Dix B. A., Smith S. A., Freudenberger J., Funke P. T. Effect of antifungal agents on lipid biosynthesis and membrane integrity in Candida albicans. Antimicrob Agents Chemother. 1987 Jan;31(1):46–51. doi: 10.1128/aac.31.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hopfer R. L., Mehta R., Lopez-Berestein G. Synergistic antifungal activity and reduced toxicity of liposomal amphotericin B combined with gramicidin S or NF. Antimicrob Agents Chemother. 1987 Dec;31(12):1978–1981. doi: 10.1128/aac.31.12.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hopfer R. L., Mills K., Mehta R., Lopez-Berestein G., Fainstein V., Juliano R. L. In vitro antifungal activities of amphotericin B and liposome-encapsulated amphotericin B. Antimicrob Agents Chemother. 1984 Mar;25(3):387–389. doi: 10.1128/aac.25.3.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kotler-Brajtburg J., Medoff G., Kobayashi G. S., Boggs S., Schlessinger D., Pandey R. C., Rinehart K. L., Jr Classification of polyene antibiotics according to chemical structure and biological effects. Antimicrob Agents Chemother. 1979 May;15(5):716–722. doi: 10.1128/aac.15.5.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lopez-Berestein G., Fainstein V., Hopfer R., Mehta K., Sullivan M. P., Keating M., Rosenblum M. G., Mehta R., Luna M., Hersh E. M. Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study. J Infect Dis. 1985 Apr;151(4):704–710. doi: 10.1093/infdis/151.4.704. [DOI] [PubMed] [Google Scholar]
  8. Lopez-Berestein G., Mehta R., Hopfer R. L., Mills K., Kasi L., Mehta K., Fainstein V., Luna M., Hersh E. M., Juliano R. Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B. J Infect Dis. 1983 May;147(5):939–945. doi: 10.1093/infdis/147.5.939. [DOI] [PubMed] [Google Scholar]
  9. Mehta R. T., Lopez-Berestein G., Hopfer R. L., Mehta K., White R. A., Juliano R. L. Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination. Antimicrob Agents Chemother. 1985 Oct;28(4):511–513. doi: 10.1128/aac.28.4.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mehta R., Lopez-Berestein G., Hopfer R., Mills K., Juliano R. L. Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta. 1984 Mar 14;770(2):230–234. doi: 10.1016/0005-2736(84)90135-4. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES