Unusual Lipid Structures Selectively Reduce the Toxicity of Amphotericin B

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-08, Vol.85 (16), p.6122-6126
Main Authors: Janoff, A. S., Boni, L. T., Popescu, M. C., Minchey, S. R., Cullis, P. R., Madden, T. D., Taraschi, T., Gruner, S. M., Shyamsunder, E., Tate, M. W., Mendelsohn, R., Bonner, D.
Format: Article
Language:English
Subjects:
550601 - Medicine- Unsealed Radionuclides in Diagnostics
Aggregation
Amphotericin B - pharmacology
Animals
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Biochemistry
Biological and medical sciences
CALORIMETRY
Calorimetry, Differential Scanning
Cell membranes
Centrifugation
COHERENT SCATTERING
DIFFRACTION
DISEASES
DRUGS
ELECTRON MICROSCOPY
Female
Freeze Etching
FUNGAL DISEASES
FUNGI
Heat measurement
INFECTIOUS DISEASES
ISOTOPES
Lethal dose 50
LIGHT NUCLEI
LIPIDS
Lipids - pharmacology
Liposomes
MAGNETIC RESONANCE
Magnetic Resonance Spectroscopy
Medical sciences
Mice
MICROSCOPY
MOLECULAR STRUCTURE
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
Pharmacology. Drug treatments
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PLANTS
RADIOLOGY AND NUCLEAR MEDICINE
RESONANCE
SCATTERING
STABLE ISOTOPES
Structure-Activity Relationship
Teeth
THERAPY
TOXICITY
X ray diffraction
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.16.6122