INTRODUCTION
Superficial cutaneous fungal infections (SCFIs) are commonly
encountered in clinical practice in the United States, and comprise infections of the skin by dermatophytes
and yeasts.1-3 Although SCFIs are seldom life threatening,
they can severely affect patients’ quality of life.1-3 The most common of the SCFIs are dermatophyte infections, which result from fungi and affect the keratinized tissues of the skin, hair, and nails.
The primary treatment for SCFIs is antifungal topical formulations.
4-5 Allylamines and azoles represent the two major classes of topical formulations that are used to treat SCFIs.4,5 Although both classes of topical formulations are clinically effective, allylamines
have fungicidal activity against dermatophytes.4,5 Conversely, the azoles are known to have greater activity against yeasts such as Candida spp and Malassezia spp, but topical allylamines have also shown to be efficacious for cutaneous
candidiasis.4,5
Allylamines inhibit squalene epoxidase, which is a vital enzyme
in the ergosterol biosynthesis pathway of fungal cell membrane formation.6 The subsequent alterations in the fungal cell membrane formation results in cellular permeability and growth inhibition.6 The allylamine antifungal agents in clinical use include naftifine, butenafine, and terbinafine.6
Azole antifungals also inhibit the synthesis of ergosterol by inhibiting the enzyme 14 alpha demethylase and thus disrupting the fungal cell membrane.6 The azole antifungal agents in clinical use contain either two or three nitrogens in the azole ring and are classified as imidazoles (eg, ketoconazole
and miconazole, clotrimazole) or triazoles (eg, itraconazole and fluconazole).6
A meta-analysis conducted by Rotta et al evaluated the efficacy of topical antifungals used in dermatophytosis treatment.7 The investigators performed a comprehensive search for randomized,
controlled trials comparing topical antifungals with one another or with placebo in dermatophytosis treatment through July 31, 2012 for all entries in MEDLINE, Cochrane Central Register
of Controlled Trials, EMBASE, Literatura Latino Americana e do Caribe em Ciências da Saúde, and International Pharmaceutical
Abstracts.7 The investigators concluded that there was not a statistically significant difference among the outcomes regarding
mycologic cure rates at the end of treatment among the various antifungals, but the allylamines naftifine, butenafine, and terbinafine are possibly the best strategies for maintaining a cured status among patients.7
Although all of the Food and Drug Administration (FDA) approved
antifungals prescribed today produce mycologic cure rates, a primary difficulty for antifungal topical drug delivery is the low diffusion rate of drugs across the stratum corneum (SC).8 The SC is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations
depends on their ability to penetrate the lipid matrix of the SC.9,10 The primary lipids found in the stratum corneum are phospholipids, cholesterol-3-sulphate, cholesterol, ceramides, sterol esters, and free fatty acids. The sebaceous lipids in the SC include triglycerides, wax esters, and squalene. 9,10
In the topical administration of antifungals, the active drug should pass the SC, particularly into the viable epidermis. Consequently,
the vehicle plays an integral role in the penetration of the active molecule into skin and ultimate clinical efficacy.11 Depending on the properties of the delivery vehicle, the penetration
of the active drug can be quite variable.12 For example,
