Development and Optimization of Itraconazole-Loaded Solid Lipid Nanoparticles for Topical Administration Using High Shear Homogenization Process by Design of Experiments: In Vitro, Ex Vivo and In Vivo Evaluation

Abstract

The aim of present study was to develop topical itraconazole (ITZ)-loaded solid lipid nanoparticles for treatment of superficial fungal infections. Formulations were prepared using high shear homogenization process, and optimized by employing a two-step design of experiments (DoE) approach. It comprised a Taguchi experimental design for screening of ‘vital few’ factors, and a central composite experimental design for optimization. Overlay of the response surface maps for percent drug entrapment (PDE), particle size, ITZ skin retention and permeation was performed to obtain the optimized ITZ-loaded SLNs (OPT-SLNs) suspension. The optimized ITZ-loaded SLNs (OPT-SLNs) showed mean particle size of (262.92 ± 8.56 nm) and zeta potential value of 22.36 mV. Excellent drug entrapment (94.21 ± 3.35%) and skin retention of ITZ (43.03 ± 1.86 μg/cm²) was achieved by OPT-SLNs. The hydrogel formulation of OPT-SLNs exhibited good gel consistency and spreadability characteristics. Pharmacodynamic and skin sensitivity studies in standardized rodent models revealed that OPT-SLNs hydrogel was more efficacious than conventional oral and topical antifungal therapies, and also safe for topical administration. Furthermore, the histoptahological evaluation depicted complete recovery of infected rats after 14-day treatment regimen of OPT-SLNs hydrogel. The developed formulation was found to have tremendous potential to enhance ITZ activity through topical administration approach.