In Vitro Nail Penetration of Tavaborole Topical Solution, 5%, Through Nail Polish on Ex Vivo Human Fingernails
July 2015 | Volume 14 | Issue 7 | Original Article | 675 | Copyright © July 2015
Tracey Vlahovic DPM,a Tejal Merchant MPharm,b Sanjay Chanda PhD,b Lee T. Zane MD,b and Dina Coronado BSb
aSchool of Podiatric Medicine, Temple University, Philadelphia, PA bAnacor Pharmaceuticals, Inc., Palo Alto, CA
BACKGROUND: Onychomycosis is a common infection of the toenails that causes nail thickening and discoloration. The physical appearance
of the infected nail can diminish self-image and negatively impact quality of life. Patients may use nail polish to mask the appearance of infected nails.
OBJECTIVE: To evaluate the in vitro nail penetration properties of tavaborole topical solution, 5%, through nail polish using ex vivo, non-diseased human fingernails.
METHODS: In study 1, tavaborole penetration was evaluated over 20 days of dosing using the Franz finite dose technique and modified
Franz diffusion cells. Nails received either 1 coat of over-the-counter (OTC) typical polish or were left unpolished (controls). In study 2, tavaborole penetration was measured over 14 days of dosing using the finite dose technique and vertical diffusion cells. Nails were polished with either 4 coats or 1 coat of salon typical polish or with 2 coats or 1 coat of OTC typical polish, or they were left unpolished.
RESULTS: In study 1, the mean ± standard deviation (SD) cumulative tavaborole penetration at day 21 was numerically higher,
though not statistically significant, through polished nails (3,526 ± 1,433 μg/cm2
) vs unpolished nails (2,661 ± 1,319 μg/cm2
). In study 2, the mean cumulative tavaborole penetration was also numerically higher (statistical significance not assessed) through all nails that received polish vs unpolished nails. At day 15, mean ± SD cumulative tavaborole nail penetration
was 1,179 ± 554 μg/cm2
through 4 coats of salon typical polish, 1,227 ± 974 μg/cm2
through 1 coat of salon typical polish, 1,493 ± 1,322 μg/cm2
through 2 coats of OTC typical polish, 1,428 ± 841 μg/cm2
through 1 coat of OTC typical polish, and
566 ± 318 μg/cm2
through unpolished nails.
CONCLUSION: Results from these in vitro studies demonstrated that tavaborole penetrated through human nails with up to 4 layers of nail polish. J Drugs Dermatol.
Onychomycosis is a common fungal infection of the nail unit, primarily caused by the dermatophytes Trichophyton
rubrum and Trichophyton mentagrophytes,1 that can cause subungual hyperkeratosis, nail plate thickening, and detachment of the nail plate from the nail bed (onycholysis). 2,3 These physical changes to the nail may lead to pain, discomfort,
difficulty in fitting into shoes, walking, or standing, and work-related challenges.1 In addition, the physical appearance of the infected nail plate contributes to embarrassment, self-consciousness, emotional distress, and diminished self-image, and may negatively impact quality of life by interfering with activities of daily living and social interactions.1,4-7
Topical antifungal therapy is an important treatment option for patients with onychomycosis; it directly targets the fungal pathogens and eliminates the potential risk for clinically significant
adverse effects and drug interactions associated with use of systemic antifungal medications.8 To eradicate the fungal
infection, a topical antifungal medication must penetrate
the nail plate and diffuse into the nail bed at concentrations required for fungicidal activity.8-10 Multiple factors affect drug penetration through the nail plate, including molecular size and hydrophilicity, formulation (eg, vehicle, pH, drug concentration, presence of chemical penetration enhancers), and properties of the nail itself (eg, inherently low permeability, thickness, hydration,
and relatively compact structure).8-10
Kerydin™ (tavaborole topical solution, 5%; Anacor Pharmaceuticals,
Inc., Palo Alto, CA) is a new-class, boron-based, small-molecule pharmaceutical approved in 2014 by the US Food and Drug Administration (FDA) for the treatment of onychomycosis
of the toenails due to the dermatophytes T. rubrum and T. mentagrophytes.11 Tavaborole is a highly specific fungal
protein synthesis inhibitor that targets fungal cytoplasmic leucyl-transfer ribonucleic acid (tRNA) synthetase (LeuRS), an aminoacyl-tRNA synthetase (AARS).11,12 The AARS family of enzymes
plays a pivotal role in maintaining and translating the genetic code within fungal DNA.12 Tavaborole binds to the ac