Topical treatments

Treatment of onychomycosis by topical methods has been met with limited success and reasons for this will be explored in more detail in Section 3. As with treating skin fungal infections such as tinea pedis (athletes foot), topical application for onychomycosis would seem the obvious choice. However, unlike the stratum corneum, the nail plate is a more difficult barrier to penetrate, requiring the drug to have much different physicochemical properties than are required for skin penetration. The two main topical treatments used today are ciclopirox and am-orolfine, both of which are formulated in lacquers that are painted onto the infected nails. The lacquer dries to leave a water-insoluble film on top of the infected nail, which then acts like a drug depot releasing the drug into the nail plate [21,22]. Tioconazole has also been used but has been largely replaced by ciclopirox and amorolfine.

Ciclopirox (4) is a hydroxypyridone antifungal agent and is believed to work by inhibiting metal dependant enzymes that degrade intracellular toxic peroxides. It does this by chelating the polyvalent cations (Fe3+ or Al3 + ) required by these enzymes [23-25]. Ciclopirox has antifungal, antibacterial and anti-inflammatory activities [25]. It is administered to the infected nails daily and due to the slow growth of nails, this treatment continues for at least 6 months. Ciclopirox has a cLogP of 2.5 and a molecular weight of 207.

Amorolfine (5) is a morpholine antifungal agent and works by inhibiting ergos-terol biosynthesis. Amorolfine is administered once or twice weekly to the infected nails for 6 to 12 months. Amorolfine has a cLogP of 5.8 and molecular weight of 317.

The relative lack of clinical efficacy seen by topical antifungal treatments has led to a substantial research effort to understand the reasons for this failure. The most common belief is that treatment failure following topical therapy for on-ychomycosis results from the inability of the drug to penetrate and disseminate throughout the nail. This topic will be explored in more depth in Sections 3 and 4. Other factors that have been implicated include lack of microbiological activity in the presence of keratin [26,27], lack of microbiological activity against the dormant dermatophytes in the nail keratin [28] and poor penetration of drug into the de-rmatophytoma, a thick mass of fungi and nail debris, that builds up between the nail plate and nail bed [29].

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