Amphotericin B-conjugated Silica-Capped Gold Nanoparticles as Antifungal Agents with improved Cellular Uptake

Abstract

Multidrug resistance is a serious menace that has resulted in several drugs or antibiotics becoming ineffective resulting in triggering toxic responses which has led to the use of nano-based carrier systems to delivery drugs or antibiotics. The broad-spectrum antifungal agent Amphotericin B (Amb) is used for treating invasive fungal infections. The conventional surfactant formulation releases Amb in a fast manner and elicits toxicity through surfactant-related mechanisms. To overcome this lacuna of the present formulations, amine-functionalized silica-capped gold nanoparticles conjugated with Amb have been designed. The structure, functionalization, size, and shape of the conjugated nanoformulation have been assessed through appropriate techniques. Around 70% Amb was found to be conjugated to the nanoparticles and they had a decent stability as indicated by the zeta potential value of –9.65 mV. Haemolysis assay confirmed the biocompatible character of the composite, possibly related to the silica capping. The cytotoxicity assays revealed that toxicity of the drug reduced confirming the hypothesis that a gradual release of Amb could overcome the lacunae of the conventional formulations. The uptake of the drug conjugate was also improved as evidenced from fluorescence microscopic and spectroscopic studies, which again can be attributed to the controlled release of Amb from the conjugate. The study suggests that the use of stable nanoparticles can improve the delivery of Amb, and can prevent biofilm formation of Candida albicans through improved uptake of Amb.