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

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.

• Authors: Qamar Zia, Aijaz Ahmed Khan, Zubair Swaleha, Mohammad Owais
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 10 Pg. 1769-90 ( 2015) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 25784804 (Publication Type: Journal Article)

Chemical References

• Antifungal Agents
• Polyglutamic Acid
• Amphotericin B

Topics

• Amphotericin B (chemistry, pharmacology, toxicity)
• Animals
• Antifungal Agents (chemistry, pharmacology, toxicity)
• Candida albicans (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Mice
• Nanoparticles (chemistry, toxicity)
• Polyglutamic Acid (chemistry, toxicity)