This work aimed to develop nanoemulsions (NE) containing cholesterol and Amphotericin B (AmB) evaluating the influence of a lipophilic amine (stearylamine; STE) on drug encapsulation efficiency (EE), cytotoxicity on macrophages and in vitro antileishmanial activity. The EE of AmB in NE was nearly 100% regardless of STE concentration. Stability studies showed that AmB-loaded NE with or without STE were stable revealing that AmB content and EE remained constant after 180days. In significant contrast, the EE for AmB in NE without cholesterol drastically decreased showing that this co-surfactant significantly improved the retention of drug in NE. The electronic absorption and circular dichroism (CD) data revealed that the signal characteristic of self-associated free AmB, the most toxic form to the host cells, was virtually absent in the spectra of AmB-loaded NE. In agreement, NE-induced toxicity toward macrophages was significantly lower than that observed for the conventional AmB. STE enhanced both cytotoxicity and the activity against intracellular amastigotes of AmB-loaded NE. However, selectivity index values for AmB-loaded NE were considerably higher than that observed for conventional AmB. AmB-loaded and cholesterol-stabilized NE constitutes an attractive alternative for the treatment of leishmaniasis.
Keywords: Amphotericin B; Antileishmanial activity; Cholesterol; Cytotoxicity; Nanoemulsion; Stearylamine.
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