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Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

Authors Zia Q, Khan AA, Swaleha Z, Owais M

Received 26 February 2014

Accepted for publication 8 May 2014

Published 5 March 2015 Volume 2015:10(1) Pages 1769—1790


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Qamar Zia,1 Aijaz Ahmed Khan,2 Zubair Swaleha,3 Mohammad Owais1

1Interdisciplinary Biotechnology Unit, 2Department of Anatomy, 3Women’s College, Aligarh Muslim University, Aligarh, India

Abstract: In the present study, we developed a self-assembled biodegradable polyglutamic acid (PGA)-based formulation of amphotericin B (AmB) and evaluated its in vitro antifungal potential against Candida albicans. The AmB-loaded PGA nanoparticles were prepared in-house and had a mean size dimension of around 98±2 nm with a zeta potential of -35.2±7.3 mV. Spectroscopic studies revealed that the drug predominantly acquires an aggregated form inside the formulation with an aggregation ratio above 2. The PGA-based AmB formulation was shown to be highly stable in phosphate-buffered saline as well as in serum (only 10%–20% of the drug was released after 10 days). The AmB-PGA nanoparticles were less toxic to red blood cells (<15% lysis at an AmB concentration of 100 µg/mL after 24 hours) when compared with Fungizone®, a commercial antifungal product. An MTT assay showed that the viability of mammalian cells (KB and RAW 264.7) was negligibly affected at AmB concentrations as high as 200 µg/mL. Histopathological examination of mouse kidney revealed no signs of tissue necrosis. The AmB-PGA formulation showed potent antimicrobial activity similar to that of Fungizone against C. albicans. Interestingly, AmB-bearing PGA nanoparticles were found to inhibit biofilm formation to a considerable extent. In summary, AmB-PGA nanoparticles showed highly attenuated toxicity when compared with Fungizone, while retaining equivalent active antifungal properties. This study indicates that the AmB-PGA preparation could be a promising treatment for various fungal infections.

Keywords: polyglutamic acid, amphotericin B, toxicity, candidiasis

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