Formulation, Optimization, and Characterization of Luliconazole-Loaded Nanostructured Lipid Carrier (NLC) Gel for Topical Antifungal Delivery

Abstract

This study successfully developed a Quality by Design (QbD)-optimized nanostructured lipid carrier
(NLC) gel to significantly enhance the topical delivery of luliconazole for deep-seated cutaneous
mycoses. Structural characterization via FTIR, DSC, and XRD confirmed complete drug
amorphization within the lipid matrix and excellent chemical compatibility. TEM imaging revealed
uniform, non-aggregated spherical nanoparticles with a hydrodynamic diameter of about 155.2 nm.
The optimized carriers were successfully dispersed into a Carbopol 940 matrix, producing a topical
gel with a physiological skin-compatible pH of 5.82 and optimal pseudoplastic (shear-thinning)
rheological behavior for ease of application. In vitro drug release profiles exhibited a distinct,
mathematically validated biphasic sustained pattern governed by anomalous, non-Fickian diffusion
(R2 = 0.9912, n = 0.62). Furthermore, ex vivo permeation studies demonstrated a superior occlusion-
driven skin hydration effect, significantly increasing localized luliconazole retention within target
epidermal and dermal layers while minimizing systemic leakage. Crucially, in vitro microbiological
assays revealed a significantly wider zone of inhibition against Candida albicans and Trichophyton
rubrum compared to commercial cream. Consequently, the formulated luliconazole NLC-gel
represents a highly effective, safe, and patient-compliant localized therapeutic strategy for managing
stubborn fungal infections.