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, 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.
Janoff
A S
AS
Liposome Company, Inc., Princeton, NJ 08540.
Boni
L T
LT
Popescu
M C
MC
Minchey
S R
SR
Cullis
P R
PR
Madden
T D
TD
Taraschi
T
T
Gruner
S M
SM
Shyamsunder
E
E
Tate
M W
MW
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D005260:Female; D005613:Freeze Etching; D008055:Lipids / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D008055:Lipids; D000666:Amphotericin B