Fractional CO₂ Laser or 40% Urea With Topical Fluconazole Microemulsion in Onychomycosis

Onychomycosis is a common fungal infection of the nails, caused by dermatophytes, non-dermatophyte molds, and yeasts. The prevalence of onychomycosis is approximately 5.5% of the global population.

Trauma of the nail, aging, nail psoriasis, genetic predisposition and chronic diseases like Diabetes mellitus, immune deficient diseases are considered risk factors for onychomycosis.

Onychomycosis is clinically classified into different types which included:

Subungual onychomycosis which may be proximal (PSO) or distal lateral (DLSO), Endonyx onychomycosis and Total dystrophic onychomycosis (TDO).

Onychomycosis is a contagious disease and will not resolve without treatment leading to deterioration in the quality of life and having the potential to be a source of wider skin infection.

Treatment of onychomycosis includes systemic therapies and topical therapies with or without physical or chemical enhancers.

Topical antifungal medications often fail due to poor nail permeability, while systemic treatments pose risks of hepatotoxicity, drug interactions, and prolonged treatment durations.

Fluconazole is a broad spectrum azole antifungal. It inhibits lanosterol-14-α-demethylase, an enzyme important for the synthesis of ergosterol, a component of fungal cell walls. Compared with other azole derivatives (e.g. ketoconazole, itraconazole, miconazole), fluconazole is less lipophilic (log P = 0.5) and has increased antifungal activity, aqueous solubility (8 mg/mL at 37°C) and higher bioavailability, due to the presence of a halogenated phenyl ring and two triazol rings. Despite its efficacy, its limited solubility and poor nail penetration hinder its topical use. Different topical forms including lipogels, amphiphilogels, hydrogels, emulsions, microemulsions, emulgels, microemulsion gels and liposomal gels have been investigated as vehicles for topical delivery of fluconazole. The topical fluconazole microemulsion-based emulgel has been found to enhance solubility, release, and adherence to the nail.

Fractional CO₂ laser is considered a physical enhancer that creates micro-channels in the nail plate, allowing deeper drug penetration. In addition, it has a direct killing effect of the fungus through photothermal damage. Furthermore, the fractional CO2 laser may contribute to inhibiting fungal growth by causing vaporization and exfoliation of the local tissue around the affected nail.

Similarly, 40% urea acts as a chemical enhancer through its keratolytic agent causing softening and thinning of the nail plate to facilitate drug permeation.

Several studies reported the efficacy of fractional CO2 laser and 40% urea in combination with several topical antifungal treatments as bifonazole and tioconazole in the treatment of onychomycosis. However, no studies have investigated or compared their efficacy in combination with topical fluconazole microemulsion yet.