title: Unusual lipid structures selectively reduce the toxicity of amphotericin B.
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.
authors.affiliation: Liposome Company, Inc., Princeton, NJ 08540.
authors.forename: A S
authors.initials: AS
authors.lastname: Janoff
authors.forename: L T
authors.initials: LT
authors.lastname: Boni
authors.forename: M C
authors.initials: MC
authors.lastname: Popescu
authors.forename: S R
authors.initials: SR
authors.lastname: Minchey
authors.forename: P R
authors.initials: PR
authors.lastname: Cullis
authors.forename: T D
authors.initials: TD
authors.lastname: Madden
authors.forename: T
authors.initials: T
authors.lastname: Taraschi
authors.forename: S M
authors.initials: SM
authors.lastname: Gruner
authors.forename: E
authors.initials: E
authors.lastname: Shyamsunder
authors.forename: M W
authors.initials: MW
authors.lastname: Tate
mesh_terms: 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
chemical_list: D008055:Lipids; D000666:Amphotericin B