Amphotericin B: A New Look at Cellular Binding

Abstract

Abstract:Objective: The binding characteristics of the polyene antifungal amphotericin B (AmB) are still arguably unclear 50 years after the first human treatment. Our purpose was to investigate the dynamic of polyene cell associated binding using an AmB directed antibody.Methods: Ex vivo murine model and in vitro mammalian cells studies were utilized to assess the binding characteristics of AmB at human therapeutic concentrations. Balb/c mice administered a single dose of an AmB formulation were assessed using immunohistochemistry. Human mononuculear cells isolated after phlebotomy were assessed using transmission electron micrography. Results & Conclusions:Ex vivo studies demonstrated diffuse binding of AmB formulations, however, the sensitivity of the technique would not allow delineation of the antifungals' cellular binding. However, transmission electron micrography of in vitro cell cultures allowed apparent discrimination of cell associated binding and suggestions of intracellular trafficking within 2 hours of polyene exposure. One could hypothesize the observed characteristics and previously published literature are suggestive of binding to clathrin type receptors with internalization and processing by endosomes. Further work will be required to substantiate this hypothesis.