Unusual lipid structures selectively reduce the toxicity of amphotericin B

Proc Natl Acad Sci U S A. 1988 Aug;85(16):6122-6. doi: 10.1073/pnas.85.16.6122.

Abstract

Ribbon-like structures result when amphotericin B interacts with lipid in an aqueous environment. At high ratios of amphotericin to lipid these structures, which are lipid-stabilized amphotericin aggregates, become prevalent resulting in a dramatic attenuation of amphotericin-mediated mammalian cell, but not fungal cell, toxicity. Studies utilizing freeze-etch electron microscopy, differential scanning calorimetry, 31P NMR, x-ray diffraction, and optical spectroscopy revealed that this toxicity attenuation is related to the macromolecular structure of the complexes in a definable fashion. It is likely that amphotericin in this specific form will have a much improved therapeutic utility.

MeSH terms

  • Amphotericin B / pharmacology*
  • Animals
  • Calorimetry, Differential Scanning
  • Female
  • Freeze Etching
  • Lipids / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Structure-Activity Relationship
  • X-Ray Diffraction

Substances

  • Lipids
  • Amphotericin B