Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation.
Pharm Res
; 34(5): 1115-1124, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-28205003
ABSTRACT
PURPOSE:
Amphotericin B (AmB) and 5-fluorocytosine (5-FC) exhibit additive to synergistic activity against systemic mycoses. Incompatibility of prescribed formulations precludes concomitant IV administration, a route with distinct advantages. Previously, we used PEG-DSPE micelles to produce a reformulation of Fungizone (AmB-SD), AmB solubilized by sodium deoxycholate, called mAmB-90. Herein, we describe a second reformulation that facilitates co-delivery of mAmB-90 and 5-FC, and evaluate the effect of PEG-DSPE micelles on the combination's activity against Candida albicans.METHODS:
We assessed the effect of 5-FC addition on the stability, in vitro toxicity, and antifungal efficacy of mAmB-90. The aggregation state and particle size of mAmB-90 combined with 5-FC (FmAmB-90) was evaluated over 48 h. Hemolytic activity was measured in vitro. Antifungal activity was determined in vitro against C. albicans. The efficacy of monotherapy and combination treatment was evaluated in a neutropenic mouse model of disseminated candidiasis.RESULTS:
The aggregation state, particle size, and hemolytic activity of mAmB-90 were unaffected by 5-FC. While antifungal activity was similar in vitro, mAmB-90 alone and combined with 5-FC was more potent than AmB-SD in vivo.CONCLUSIONS:
Short-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Cloreto de Sódio
/
Anfotericina B
/
Flucitosina
/
Antifúngicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article