title: Novel biodegradable poly(gamma-glutamic acid)-amphotericin B complexes show promise as improved amphotericin B formulations.
abstract: 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®) and liposomal AmB (AmBisome®). 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 °C and 25 °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®but comparable to AmBisome®, with respect to the hemolytic activity and the modulation of pro-inflammatory cytokines (TNF-α and IL-1ß). In-vivo, AmB/PGGA complexes were significantly more efficacious than both Fungizone®and AmBisome®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.
authors.affiliation: UCL School of Pharmacy, University College London, London, UK.
authors.forename: Tan
authors.initials: T
authors.lastname: Dinh
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Zia
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Swaleha
authors.initials: S
authors.lastname: Zubair
authors.affiliation: UCL School of Pharmacy, University College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Stapleton
authors.affiliation: UCL School of Pharmacy, University College London, London, UK.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Singh
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India. Electronic address: owais_lakhnawi@yahoo.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Owais
authors.affiliation: UCL School of Pharmacy, University College London, London, UK. Electronic address: s.somavarapu@ucl.ac.uk.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002177:Candidiasis / Q000188:drug therapy; D018698:Glutamic Acid; D051379:Mice; D036103:Nanotechnology / Q000379:methods; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000935:Antifungal Agents; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D000666:Amphotericin B
keywords: AmB/PGGA complexes; Amphotericin B; Fungizone(®) and AmBisome(®); Poly(gamma-glutamic acid); Toxicity