In vitro/in vivo evaluation of statistically engineered alginate scaffold reinforced with dual drugs loaded silica nanoparticles for enhanced fungal therapeutics

Abstract

In the current study, sustained release salicylic acid (SA) and ketoconazole (KCZ) loaded silica nanoparticles (SiO2-NPs) were encapsulated in natural macromolecule-alginate (ALG) based scaffold through freeze gelation method for an effective treatment of commonly prevailed fatal fungal infections. After statistical optimization by central composite rotatable design (CCRD), the optimized scaffold was subjected to comparative in vitro/in vivo antifungal, skin irritation, wound healing, cytotoxicity, and histopathological evaluations. In physico-chemical characterization performed through X-ray diffraction (p-XRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA), an absolute lack of structural interactions was found between drugs and formulation components. The zeta potential and scanning electron microscopy (SEM) revealed spherical, highly porous negatively charged (–23.1) SiO2-NPs having a size distribution of 40–80 nm with successful encapsulation in negatively charged scaffold (-20.2 mV). The entrapment efficiency and drugs release exhibited visible quadratic influence of formulation variables on scaffold. The optimized ALG-scaffold demonstrated comparatively an enhanced in vitro, in vivo antifungal activity, least cytotoxicity and rapid wound healing efficacy in histopathological evaluation by sustained drugs release up to 14-days without any skin irritation effect. The study suggested the potential of alginate scaffold for not only the endurance of drugs loaded SiO2-NPs but also for the simultaneous co-delivery of medicaments fulfilling the need of consistent prolonged availability of drugs for better fungal therapeutics.

Keywords

• Alginate
• Central composite design
• Fungal therapeutics
• Ketoconazole
• Salicylic acid
• Silica nanoparticles