Drug Delivery to the Nail: Therapeutic Options and Challenges for Onychomycosis

Abstract

Onychomycosis is one of the most common nail disorders. It affects 10-30% of the world population and is caused by dermatophytes, non-dermatophytes, molds, and yeasts. Present treatment methods of onychomycosis include oral therapy, topical therapy, and a combination of both; they have mild-to-moderate efficacy, with a relapse and reinfection rate of 20-25%. For oral therapy, newer antifungal compounds (azole class and allylamine class) are being investigated to increase efficacy and minimize side effects. Oral therapy with antifungal agents have severe side effects, with lesser bioavailability and longer duration of treatment. By contrast, topical therapy of onychomycosis is associated with greater patient compliance and fewer systemic side effects and drug interactions. Current topical treatment options of onychomycosis are nail lacquers, ointments, lotions, solutions, and gels, but these formulations have been unsuccessful due to poor penetration and distribution of drugs at the infected site. Therefore, novel therapeutic options are constantly being researched to improve the efficacy of onychomycosis treatment by enhancing the permeation of the drug across the nail to reach the infected site. Various physical and chemical enhancement methods have been studied to increase the permeation of drugs across the nail plate to the nail bed. Device-based therapeutic options have also been investigated to increase the antifungal drug concentration and its effects in the onychomycotic nail. Randomized clinical trials of these novel therapies have demonstrated better efficacy. The present review discusses the anatomy of the human nail, onychomycosis and its types, onycholysis, and conventional and novel therapies. We also review patents granted as well as design challenges facing optimal drug formulation for onychomycosis treatment.

In Vitro Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis

“…Molecular weight (MW) and keratin-binding affinity are important factors for nail penetration (5). Drugs with either high keratin affinity or a molecular weight of over 300 have difficulty penetrating the nail plate and reaching the nail bed (11). Similarly, this study showed that drugs with a molecular weight of over 300, such as efinaconazole (MW, 348.4) and amorolfine (MW, 317.5), were found at a drug concentration of less than 4,000 g/g in the upper nail layer.…”

An investigation of how fungal infection influences drug penetration through onychomycosis patient’s nail plates

“…The prevalence of onychomycosis has been estimated at around 5% in Western countries and has continued to increase in recent decades [3] , [4] , [5] , [6] , [7] , [8] , [9] . It is important to treat onychomycosis as it is an infection that does not resolve spontaneously, and it may cause pain and can substantially reduce the quality of life of patients [10] , [11] . In addition, if left untreated the infection may worsen, spread to other uninfected locations (other nails or to the surrounding skin) or infect other patients.…”

Effect of monoterpenes on ex vivo transungual delivery of itraconazole for the management of onychomycosis

“…Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, mold, and yeast and is the most common nail disorder seen in clinical practice, affecting 10%‐30% of the world population . It is an important problem, as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions .…”