Dinh, T;
Zia, Q;
Zubair, S;
Stapleton, P;
Singh, R;
Owais, M;
Somavarapu, S;
(2017)
Novel biodegradable poly(gamma-glutamic acid)–amphotericin B complexes show promise as improved amphotericin B formulations.
Nanomedicine: Nanotechnology, Biology and Medicine
, 13
(5)
pp. 1773-1783.
10.1016/j.nano.2017.02.003.
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Abstract
Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues or high production costs. AmB complexes based on poly(gamma-glutamic acid) (PGGA) have been prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone®) and liposomal AmB (AmBisome®). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (−51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a theoretical drug loading (up to 76.9%). In vitro, AmB/PGGA complexes exhibited an improved and comparable cytotoxicity profile as compared with Fungizone® and AmBisome® respectively, with respect to hemolytic activity and up-regulation of cytokine productions (TNF-α and IL-1ß). AmB/PGGA complexes were significantly more efficacious in vivo than both Fungizone® and AmBisome® in experimental murine candidiasis. These results provide strong evidence that AmB/PGGA complexes have a better efficacy and safety profile than the currently approved AmB products.
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