Browse by author
Lookup NU author(s): Dr Bushra alQuadeib,
Professor Lidija Siller,
Professor Matthew Wright,
Dr Ben Horrocks
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p < 0.05) improved the bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.
Author(s): Radwan MA, AlQuadeib BT, Siller L, Wright MC, Horrocks B
Publication type: Article
Publication status: Published
Journal: Drug Delivery
Online publication date: 03/02/2017
Acceptance date: 22/08/2016
Date deposited: 06/02/2017
ISSN (print): 1071-7544
ISSN (electronic): 1521-0464
Publisher: Taylor & Francis Inc.
Notes: This articles is published with Open access
Altmetrics provided by Altmetric