Amphotericin B (AmB) is an effective antifungal drug used for the treatment of severe systemic fungal infections. This drug is known for aggregating in aqueous solutions, yet the impact of aggregation on drug toxicity is not fully understood. In clinical formulations, AmB is often mixed with different combinations of lipids to control aggregation; specifically, an H-aggregate species present in AmB and water solutions, but reduced in the presence of the lipid complexes. The degree of aggregation is controlled by drug attachment mechanisms, dependent on the various sizes and shapes of the lipid complexes. To better understand the link between aggregation and drug behavior, clinical versions of AmB and lipid constructs were synthesized and characterized spectroscopically. UV-Vis absorption is critical in assessing aggregation as the H-aggregate appears or lessens. Differential interference contrast microscopy assess size and shape. The next step will be to incubate the AmB formulations with live yeast cells and image their interactions using transient absorption microscopy. Comparative analysis of clinical formulations with native AmB and yeast interactions may yield a better understanding of how the different complexes work efficiently to kill fungi, with or without aggregating.

Investigating the impact of lipid formulations on the aggregation and behavior of amphotericin B

255th National Meeting (2018)

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