In vitrosynergistic antifungal evaluation through combination of F127-conjugated amphotericin B and curcumin-loaded micelles

Amphotericin B (AmB) coupled with hydrophilic or amphiphilic polymers and combined with natural active products should be an effective way to improve biosafety and dose-reduced activity of AmB against C. albicans. In the study, F127-AmB conjugate was synthesized through O- and N-alkylation with AmB and F127 as starting materials, and its hemolytic, aggregation and release behavior were evaluated. Curcumin-loaded micelles (Cur-M) were prepared to study its synergistic effect with F127-AmB conjugate micelles. It was found that AmB in F127-AmB mainly existed as monomers without hemolysis, suggesting its good biosafety to host. The in vitrorelease of AmB from the F127-AmB conjugate micelles was slow and sustained, and similar release property was observed for Cur-M. The anticandidal activity of F127-AmB conjugate micelles alone was good and similar to that of native AmB alone. However, the F127-AmB conjugate micelles showed strong synergism with Cur-M with fractional inhibitory concentration index value of 0.0936. The combination of both Cur-M and F127-AmB conjugate micelles not only significantly boosted the biofilm inhibition activity of F127-AmB conjugate micelles, but also caused C. albicansapoptosis at low concentration. So, combination of the conjugated AmB micelles and Cur-loaded micelles was a noteworthy strategy to improve AmB's antifungal activity and safety.