Protective effect of histatin 5 and amphotericin B conjugated nanostructures in C. albicans challenged Swiss albino mice.

Abstract

This study explores the development of silica-gold nanostructures conjugated with histatin 5 (H5) and amphotericin B (A_mpB) for the management of Candida albicans-induced candidiasis. H5 and A_mpB were covalently attached to the silica-gold nanostructures (ASi_np-GN) using EDC-NHS chemistry, with fluorescent FITC labeling employed in a parallel experiment to study nanostructure localization. Characterization techniques, including UV-Vis spectroscopy, dynamic light scattering, zeta potential analysis, fluorescence spectroscopy, differential scanning calorimetry, thermogravimetric analysis, high-resolution transmission electron microscopy, atomic force microscopy, and drug release studies, confirmed the successful conjugation and stability of the nanostructures. Biological evaluations using C. albicans demonstrated a minimum inhibitory concentration (MIC50) of 5.42 μM for A_mpB in the nanostructures, along with enhanced localization as observed via fluorescence microscopy. The nanostructures effectively inhibited biofilm formation and showed high biocompatibility in hemolysis and MTT assays. In vivo studies using a disseminated candidiasis model in Swiss albino mice revealed significant therapeutic efficacy, evidenced by reduced C. albicans burden, decreased A_mpB toxicity, improved heart function, and preserved tissue integrity. These results highlight the role of H5 conjugation in targeted drug delivery, enhancing the therapeutic potential of A_mpB while minimizing adverse effects, making it a promising approach for candidiasis management. However, a detailed pharmacokinetic investigation on the use of these nanostructures is warranted before taking this to the clinical side.