Characterization and Time Dependence of Amphotericin B: Deoxycholate Aggregation by Quasielastic Light Scattering

Abstract

Quasielastic light scattering measurements of amphotericin B (AB):deoxycholate (DOC) preparations provided information about particle size and aggregation as a function of concentration. The data allowed the time dependence of the aggregation to be followed and indicated that the initial rates of the change in average equivalent hydrodynamic diameter increased with decreasing concentration. The results extend the model proposed by Lamy-Freund and co-workers, which describes AB:DOC systems as consisting of AB:DOC mixed aggregates co-existing with pure DOC micelles. Although the AB:DOC aggregates are unstable at all concentrations studied, the rate of aggregation increases by three orders of magnitude as the concentration is reduced from 20mM (DOC concentration) to the concentration region of DOC micellization. These results are in agreement with the different distribution of AB and DOC in the body of experimental animals, and may be of relevance for the understanding of the serious toxic effects of AB.