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Novel biodegradable poly(gamma-glutamic acid)–amphotericin B complexes show promise as improved amphotericin B formulations

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. Green open access

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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.

Type: Article
Title: Novel biodegradable poly(gamma-glutamic acid)–amphotericin B complexes show promise as improved amphotericin B formulations
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.nano.2017.02.003
Publisher version: http://dx.doi.org/10.1016/j.nano.2017.02.003
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Amphotericin B; Poly(gamma-glutamic acid); AmB/PGGA complexes; Fungizone® and AmBisome®; Toxicity
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > SoP Pharmaceutical and Bio Chemistry
URI: http://discovery.ucl.ac.uk/id/eprint/1554715
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