title: Nanoemulsions loaded with amphotericin B: a new approach for the treatment of leishmaniasis.
abstract: 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.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Leila Rodrigues
authors: LR
authors: Caldeira
authors: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Flaviana Ribeiro
authors: FR
authors: Fernandes
authors: Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Daniel Ferreira
authors: DF
authors: Costa
authors: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Frédéric
authors: F
authors: Frézard
authors: Department of Biological Sciences, Institute of Biological and Exact Sciences, Federal University of Ouro Preto (UFOP), Morro do Cruzeiro, 35400-000 Ouro Preto, Minas Gerais, Brazil.
authors: Luís Carlos Crocco
authors: LC
authors: Afonso
authors: Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: lucas@farmacia.ufmg.br.
authors: Lucas Antônio Miranda
authors: LA
authors: Ferreira
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry*; D002460:Cell Line; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry; D004655:Emulsions; D007891:Leishmania / Q000187:drug effects* / Q000502:physiology; D007896:Leishmaniasis / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D004655:Emulsions; D000666:Amphotericin B; D002784:Cholesterol
keywords: Amphotericin B; Antileishmanial activity; Cholesterol; Cytotoxicity; Nanoemulsion; Stearylamine