title: 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.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Zia
authors.affiliation: Department of Anatomy, Aligarh Muslim University, Aligarh, India.
authors.forename: Aijaz Ahmed
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Women's College, Aligarh Muslim University, Aligarh, India.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Swaleha
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Owais
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011099:Polyglutamic Acid / Q000737:chemistry / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D011099:Polyglutamic Acid; D000666:Amphotericin B
keywords: amphotericin B; candidiasis; polyglutamic acid; toxicity