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