Comparative immunotoxicity evaluation of amphotericin B and ABELCET, an amphotericin B lipid complex (ABLC).
ABELCET, an amphotericin B lipid complex formulation (ABLC) and an aqueous, non-lipid-containing formulation with sodium deoxycholate (AmBd), were evaluated for their potential to induce immunotoxicity in B6C3F1 female mice. ABLC was administered intravenously at doses of 1, 3, and 10 mg/kg daily for 28 days, while AmBd at 1 mg/kg was administered by the same route and duration. The effect of ABLC and AmBd on clinical signs, body weight, and spleen weight was determined. Peritoneal macrophage function was measured by phagocytosis of 51Cr-labeled chicken red blood cells and generation of hydrogen peroxide during respiratory burst. The ability of natural killer cells to lyse radiolabeled tumor target cells was evaluated in a short-term chromium-release assay. The ability of splenic T and B cells to undergo blastogenesis and of splenic T cells to recognize alloantigens present on foreign cells was assessed in a splenic lymphocyte assay and the ability of mice to generate antibody-forming cells following immunization with sheep red blood cells was measured. Neither ABLC nor AmBd affected the metabolic or functional activity of murine phagocytic cells. These agents also did not cause any biologically significant or dose-related changes in B- or T-cell responses to mitogens, T-cell responses to allogeneic cells in the mixed lymphocyte culture assay, or natural killer cell function. The ability to generate a primary antibody response to a T cell-dependent antigen was also unimpaired. Based on the results of this study, it was concluded that neither ABLC at dose up to 10 mg/kg nor AmBd at dose up to 1.0 mg/kg produce biologically significant immunologic changes in B6C3F1 mice.
Zhang
Zhihua
Z
Enzon Pharmaceuticals, Inc., Piscataway, New Jersey 08854, USA. john.zhang@enzon.com
Lipman
Jack M
JM
Diener
Robert M
RM
Thomas
Peter
P
D000666:Amphotericin B / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004338:Drug Combinations; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D010713:Phosphatidylcholines / Q000633:toxicity*; D010715:Phosphatidylglycerols / Q000633:toxicity*; D012756:Sheep; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D004338:Drug Combinations; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008934:Mitogens; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D003208:Concanavalin A; D000666:Amphotericin B; D006861:Hydrogen Peroxide