Bioinspired Nanostructured Lipid Carriers Functionalized with Keratin-Binding Peptides for Enhanced Transungual Delivery of Efinaconazole

Abstract

In order to improve the transungual delivery of efinaconazole through nail keratin for the topical treatment of onychomycosis, this study sought to create bioinspired nanostructured lipid carriers (NLCs) functionalized with keratin-binding peptides. NLCs were formulated using the solvent evaporation technique with stearic acid and oleic acid, optimized via Box–Behnken Design (BBD), and surface-engineered using a decorin-derived peptide to mimic natural keratin-binding mechanisms. Characterization studies showed that it outperformed the plain drug (90 ± 2% release in 24 hours) by having a particle size of 120 ± 6 nm, an entrapment efficiency (EE) of 88 ± 2%, and a sustained drug release of 75 ± 3% over 72 hours. A depth of 1.2 ± 0.1 mm was found in in vitro nail penetration studies, which is almost twice as deep as unmodified NLCs (0.5 ± 0.1 mm, p < 0.005, one-way ANOVA). In antifungal tests against Candida albicans, the bioinspired NLCs' zone of inhibition (ZOI) was 28 ± 2 mm, while the plain NLCs' was 20 ± 1 mm (p < 0.005). Topical safety was supported by skin irritation studies that used the Draize test, which showed non-irritancy (score: 0.7 ± 0.2). These findings demonstrate how bioinspired NLCs may be used as a new, secure, and effective way to increase drug penetration through nail keratin and, consequently, improve treatment outcomes for fungal nail infections.