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Comparative Study | Journal Article

Heat-induced superaggregation of amphotericin B reduces its in vitro toxicity: a new way to improve its therapeutic index.

F Gaboriau, M Chéron, C Petit, J Bolard
F Gaboriau
Laboratoire de Physicochimie Biomoléculaire et Cellulaire (CNRS UA 2056), Université P. et M. Curie, Paris, France. gaboriau@wanadoo.fr
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M Chéron
Laboratoire de Physicochimie Biomoléculaire et Cellulaire (CNRS UA 2056), Université P. et M. Curie, Paris, France. gaboriau@wanadoo.fr
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C Petit
Laboratoire de Physicochimie Biomoléculaire et Cellulaire (CNRS UA 2056), Université P. et M. Curie, Paris, France. gaboriau@wanadoo.fr
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J Bolard
Laboratoire de Physicochimie Biomoléculaire et Cellulaire (CNRS UA 2056), Université P. et M. Curie, Paris, France. gaboriau@wanadoo.fr
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DOI: 10.1128/AAC.41.11.2345
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ABSTRACT

Superaggregation of amphotericin B (AmB) was previously shown to occur upon heating of solutions at 70 degrees C. In the present study, we demonstrate that heat pretreatment of Fungizone (deoxycholate salt of AmB [AmB-DOC]) solutions induces a drastic decrease in the in vitro toxicity of this antibiotic. Heated AmB-DOC colloidal solutions, which mainly contained superaggregated and monomeric forms of the antibiotic, were strongly less hemolytic than unheated solutions (aggregates and monomers). Thermal pretreatment of AmB-DOC solutions also reduced the toxicity to the cell line HT29, as deduced from two simultaneous cell viability assays (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release). These heated colloidal solutions were only slightly less efficient than the unheated ones at inhibiting the growth of Candida albicans cells in vitro. Such results suggest that mild heat treatment of AmB-DOC solutions could provide a new and simple solution for improving the therapeutic index of this antifungal agent by reducing its toxicity to mammalian cells.

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Heat-induced superaggregation of amphotericin B reduces its in vitro toxicity: a new way to improve its therapeutic index.
F Gaboriau, M Chéron, C Petit, J Bolard
Antimicrobial Agents and Chemotherapy Nov 1997, 41 (11) 2345-2351; DOI: 10.1128/AAC.41.11.2345

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Heat-induced superaggregation of amphotericin B reduces its in vitro toxicity: a new way to improve its therapeutic index.
F Gaboriau, M Chéron, C Petit, J Bolard
Antimicrobial Agents and Chemotherapy Nov 1997, 41 (11) 2345-2351; DOI: 10.1128/AAC.41.11.2345
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