Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 5, Pages 1773-1783Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.02.003
Keywords
Amphotericin B; Poly(gamma-glutamic acid); AmB/PGGA complexes; Fungizone((R)) and AmBisome((R)); Toxicity
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Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues and high production costs. In this study, AmB complexes based on poly(gamma-glutamic acid) (PGGA) were prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone((R))) and liposomal AmB (AmBisome((R))). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-45.5 to -51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 degrees C and 25 degrees C), and have a high drug loading (up to 35% w/w). In vitro, AmB/PGGA complexes exhibited a more favorable cytotoxicity profile than Fungizone((R)) but comparable to AmBisome((R)), with respect to the hemolytic activity and the modulation of pro-inflammatory cytokines (TNF-alpha and IL-1 beta). In-vivo, AmB/PGGA complexes were significantly more efficacious than both Fungizone((R)) and AmBisome((R)) against experimental murine candidiasis. These results provide strong evidence that AmB/PGGA complexes display better efficacy and safety features than the currently approved AmB products. (c) 2017 Elsevier Inc. All rights reserved.
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