Investigation on utility of some novel terpenes on transungual delivery of fluconazole for the management of onychomycosis

Onychomycosis, the most prevailing affliction of the nail, accounts for approximately 90% of the toenail infection worldwide. Owing to this infection, the affected patients experience reduced quality of their life as its awful appearance undermines their daily activities and social interactions. Onychomycosis is notoriously strenuous to cure. Systemic therapy, though effective, possess severe complication of toxicities, contra-indication, and drug-drug interaction. Albeit topical therapy is favorable to its localized effect, its potency relates to the effective concentration of the antifungal drugs achieved at the infection site. An approach to accomplish this goal would be acquiring benefits from the terpenes as penetration enhancers from natural sources. This investigation aimed to study the effectiveness of six terpenes, namely safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, as potential penetration enhancers for improved nail permeation of fluconazole through the human nail.Ex vivo permeation experiments were carried out by soaking the nail clippings of human volunteers in control and working solutions containing fluconazole (5 mg/ml) per se and fluconazole (5 mg/ml) with 6% of each terpene, including safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, respectively, for 48 h. The amount of fluconazole in nail clippings was quantified using an HPLC method.Statistical analysis showed that fluconazole transungual permeation was influenced by the studied terpenes in the following order: safranal >lavandulol acetate >limonene > rose oxide (p-value >0.05) while the other terpenes showed no significant difference with the control group and safranal represents as the most effective permeation enhancer for the transungual delivery of fluconazole.It is concluded that the safranal can be successfully used as a safe and potential permeation enhancer to enhance the transungual delivery of fluconazole for the treatment of onychomycosis.