NDLI: Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation

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Antifungal Efficacy of an Intravenous Formulation Containing Monomeric Amphotericin B, 5-Fluorocytosine, and Saline for Sodium Supplementation

Content Provider	Semantic Scholar
Author	Alvarez, Celeste Andes, David R. Kang, Jeong Yeon Krug, Carmen Kwon, Glen S.
Copyright Year	2017
Abstract	PurposeAmphotericin 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.MethodsWe 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.ResultsThe 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.ConclusionsShort-term stability and in vivo efficacy of our formulation suggest potential to simultaneously deliver AmB and 5-FC for potent antifungal efficacy.
Starting Page	1115
Ending Page	1124
Page Count	10
File Format	PDF HTM / HTML
DOI	10.1007/s11095-017-2121-7
PubMed reference number	28205003
Journal	Medline
Volume Number	34
Alternate Webpage(s)	http://www.medicine.wisc.edu/sites/default/files/antifungal_efficacy_of_an_intravenous_andes_2_15_17.pdf
Alternate Webpage(s)	https://doi.org/10.1007/s11095-017-2121-7
Journal	Pharmaceutical Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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