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.

Biomimetically engineered Amphotericin B nano-aggregates circumvent toxicity constraints and treat systemic fungal infection in experimental animals

“…3A ) was comparable to that of AmBisome 9 . The biphasic pattern of drug release observed is analogous to that reported for other lipidic and polymeric carrier based reservoirs of AmB 69 , 70 . Since in-vivo stability in biological fluid is an important criterion for its future use, change in AmB-NA drug content in the presence of serum was monitored over the time.…”

“…The vitro release of AmB from AmB-NAs in surrounding milieu (PBS, Histidine buffer and serum) was evaluated following published protocol 69 as standardized in our lab.…”

Sol-gel synthesis of thorn-like ZnO nanoparticles endorsing mechanical stirring effect and their antimicrobial activities: Potential role as nano-antibiotics

“…MIC was defined as the minimum concentration of ZnO-NPs at which there was no visible growth of the test pathogens28. Details of these procedures have been provided in the supplementary section.…”

“…CLSI (formerly NCCLS) broth dilution method 26 27 was utilized for determining the MIC values against Candida and bacterial pathogens. MIC was defined as the minimum concentration of ZnO-NPs at which there was no visible growth of the test pathogens 28 . Details of these procedures have been provided in the supplementary section .…”

<p>Targeted Therapy for Hepatocellular Carcinoma: Co-Delivery of Sorafenib and Curcumin Using Lactosylated pH-Responsive Nanoparticles</p>

“…SFN and CCM co-delivered, pH-responsive lactosylated nanoparticles (LAC-SFN/CCM-NPs) were self-assembled by using the nanoprecipitation technique. [32][33][34] Briefly, SFN (50 mg) and CCM (50 mg) were dissolved in acetone (5 mL) (solution 1), LAC-ADH-PEG-PCL (200 mg) was dissolved in ethyl alcohol (10 mL) (solution 2). Then, solution 1 and 2 were added dropwise to deionized water (35 mL) under constant stirring.…”