Effect of Amphotericin B on the thermodynamic stability, aggregation state, hemolysis and antifungal activity of Amphotericin B-nonionic surfactant micellar system

Abstract

Amphotericin B (AmB) is a toxic and low solubility antifungal drug. In this paper, AmB was encapsulated by different nonionic surfactants and the effect of their structures on AmB was investigated. Three micellar systems were prepared: AmB/HS15, AmB/TW80, and AmB/ELP micellar systems. The interfacial and micellization behaviours of the three micellar systems were investigated. The critical micelle concentration (CMC) of different nonionic surfactant micelles was calculated and discussed independently. The results showed that the ELP molecules with three hydrophobic chains reduced the CMC value of the systems, contributing to the formation of drug-laden micelles. In addition, some interfacial and thermodynamic parameters were calculated and analyzed. On this basis, the particle size, aggregation number, transmittance, and in vitro release of each system were further determined, and the findings revealed that AmB/ELP micellar systems had more physical stability than AmB/TW80 and AmB/HS15 micellar systems, and all three micelle systems exhibited slow release properties. The AmB/ELP micellar system had a lower hemolytic toxicity than the AmB/TW80 and AmB/HS15 micellar systems in terms of hemolysis. The antifungal activity of the AmB/TW80 micellar system was reduced due to the large spatial resistance of the hydrophilic segment of the TW80 molecule, which prevented its binding with ergosterol, making the antifungal activity of the AmB/TW80 micellar system much lower than that of the AmB/ELP and AmB/HS15 micellar systems. In summary, different nonionic surfactant structures have a significant impact on the toxicology and pharmacology of AMB, which provides new research ideas for the development of new dosage forms.