A new nanoemulsion formulation improves antileishmanial activity and reduces toxicity of amphotericin B

作者：Moreira dos Santos Delia Chaves; Silverio de Souza Marselle Leite; Teixeira Eliane Morais; Alves Lindicy Leidicy; Carneiro Vilela Jose Mario; Andrade Margareth; Carvalho Maria das Gracas; Fernandes Ana Paula; Miranda Ferreira Lucas Antonio; Gontijo Aguiar Marta Marques

来源：Journal of Drug Targeting, 2018, 26(4): 357-364.

DOI：10.1080/1061186X.2017.1387787

• Nanoemulsion
• amphotericin B
• visceral leishmaniasis
• haemolytic toxicity
• antileishmanial activity

This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL). When the NE was submitted to gradual increases in pressure, the PI values and droplet size decreased. The droplet size (similar to 145nm) was lower than that obtained in previous studies. The zeta potential was negative and the EE was almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB-loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at 2mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same dose, did not result in any sign of acute toxicity, promoting a significant reduction in parasite burden as compared to the C-AmB. These findings suggest that this new AmB-loaded NE constitutes an attractive alternative for the treatment of VL due to improved efficacy and lower toxicity.

• 出版日期2018