Molecular Docking-Guided Ungual Drug-Delivery Design for Amelioration of Onychomycosis

The present work envisaged an adherent luliconazole-loaded bilayer nail lacquer (BNL) with significant transungual activity. The locally applied sustained-release BNL formulation was designed for an improved retention, payload, and final dermatokinetic disposition. A primary step in the fabrication of a BNL included overcoming of physical barriers like a-keratin (also alpha-keratin), a protein present in human nails, and then allowing the drug molecule to permeate at the site of action. Although luliconazole is an established antifungal agent, has limited clinical exploitation for its use in treating onychomycosis. An in silico study elucidating its interaction with lanosterol-14-alpha demethylase, an enzyme which is the key region of drug action mechanism, was highly supportive of its imminent clinical potential. Optimization of prepared BNL formulations via response surface modeling (Box-Behnken Design-Expert 10.0.6) logically ascertained the effect of selected independent variables and showcased its effect via dependent responses. Surface morphology of the prepared BNL films was well corroborated for the presence of two distinct polymeric layers through scanning electron microscopy imaging. Nail permeation studies revealed a cumulative drug release of 71.25 +/- 0.11% through bovine hooves up to 24 h. Luliconazole while exposing antifungal activity against clinical isolates of Trichophyton rubrum in agar cup-plate method disclosed a 38 mm diameter zone of inhibition. Further, the optimized BNL exhibited a bioadhesive force of 1.9 +/- 0.11 N, which assured its retention on the nail surface for prolonged duration of time. In Conclusion, it is deduced that the conventional treatment modalities for onychomycosis require circumvention of certain pharmacotechnical caveats. Therefore, in the present study, a multipronged BNL system was proposed, which negates the need of frequent drug application, improvises cosmetic appearance, yields fruitful therapeutic outcomes, and has a clinical supremacy over the available therapeutics.