Development and In-Vitro Characterization of a Phytochemical-Enriched Nail Lacquer from Lawsonia inermis Extract for the Management of Onychomycosis

Abstract

Onychomycosis is notoriously difficult to treat because the dense, keratinized nail plate limits topical drug penetration. Plant-based antifungals could expand safe, accessible options if formulated to cross the ungual barrier. This study developed a hydroalcoholic, hydroxypropyl-chitosan (HPCH) nail lacquer enriched with Lawsonia inermis (henna) leaf extract standardized to lawsone (2-hydroxy-1,4-naphthoquinone). Five lacquer prototypes (F1–F5) varied in HPCH (2–4% w/v) and keratolytic enhancers (urea 0–10% w/v; thioglycolic acid 0–1% w/v). Extract was characterized by HPLC and total phenolics; lacquers were evaluated for viscosity, drying time, non volatile content, film thickness, adhesion, water resistance, drug content, in-vitro antifungal activity against Trichophyton rubrum, T. mentagrophytes, and Candida albicans (CLSI M38-A2 broth microdilution), and transungual permeation across hydrated human nail clippings in Franz cells. The optimized formula (F4: HPCH 3%, urea 10%, thioglycolic acid 0.5%) showed rapid “dry-to-touch” (6.2 ± 0.5 min), high non-volatile content (24.8 ± 0.7%), robust adhesion, and the greatest 24 h permeation (lawsone 21.4 ± 1.8 µg cm⁻²), significantly exceeding enhancer-free F1 (7.6 ± 0.9 µg cm⁻²; p < 0.001). F4’s eluted film produced MIC ranges of 62.5–125 µg mL⁻¹ (extract equivalent) for dermatophytes and 125 µg mL⁻¹ for C. albicans, with ≥3-log kill at 24 h. Cytotoxicity on HaCaT keratinocytes yielded IC₅₀ = >500 µg mL⁻¹ (selectivity index ≥4). Findings support HPCH-based, lawsone-standardized lacquers with keratolytic enhancers as promising candidates for topical onychomycosis therapy, warranting ex-vivo infected nail and clinical studies. Background and methods align with current transungual guidelines and literature on nail lacquers, enhancers, and lawsone pharmacology.