Iontophoretic Drug Delivery across Human Nail

Murthy, S. Narasimha; Wiskirchen, Dora E.; Bowers, Christopher Paul

doi:10.1002/jps.20757

Cited by 84 publications

(18 citation statements)

References 22 publications

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“…To be effective, an adequate amount of drug must penetrate the nail bed (7) and remain active within the keratin matrix of the nail and nail bed (8)(9)(10). The unique properties of the nail, particularly its thickness and relatively compact construction, make it a formidable barrier to the entry of topically applied agents (11).…”

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confidence: 99%

“…The upper dorsal layer is only a few cell layers thick but consists of hard keratin, constituting the main barrier for drug diffusion into and through the nail plate (12). Further, many antifungal agents bind strongly to keratin, which not only restricts their penetration through the nail but may also reduce their antifungal activity (8)(9)(10). Keratinbound drugs do not contribute to a concentration gradient, resulting in the accumulation of topically applied drug in the surface nail layers and decreased penetration to the deeper layers and nail bed (8).…”

mentioning

confidence: 99%

“…Further, many antifungal agents bind strongly to keratin, which not only restricts their penetration through the nail but may also reduce their antifungal activity (8)(9)(10). Keratinbound drugs do not contribute to a concentration gradient, resulting in the accumulation of topically applied drug in the surface nail layers and decreased penetration to the deeper layers and nail bed (8). Thus, low keratin affinity is considered a desirable physicochemical property of drugs for topical treatment of onychomycosis and possibly of other superficial mycoses.…”

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confidence: 99%

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The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

Sugiura

Sugimoto

Hosaka

et al. 2014

Antimicrob Agents Chemother

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Onychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dose in vitro studies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth of Trichophyton rubrum under the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity against Trichophyton mentagrophytes comparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes infection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis.

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The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

Sugiura

Sugimoto

Hosaka

et al. 2014

Antimicrob Agents Chemother

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“…5 The clinical significance of formulations such as medicated nail lacquers, patches and creams for topical treatment of onychomycosis is debatable. New techniques such as use of chemical penetration enhancers, 7–10 micro-drilling, 11 nail abrasion, 12–14 acid etching 15 and iontophoresis 16–24 are also being evaluated as potential treatment methods for onychomycosis. The drug-device combination which uses iontophoresis to deliver high concentrations of medication directly to the site of action has considerable potential to improve the treatment of onychomycosis.…”

Section: Introductionmentioning

confidence: 99%

“…The drug-device combination which uses iontophoresis to deliver high concentrations of medication directly to the site of action has considerable potential to improve the treatment of onychomycosis. 16–24 Although significant efforts have been made to evaluate and enhance transungual iontophoretic drug delivery, little has been done to systematically characterize ion transport across the nail plate. It is fair to say that work to date on transungual ion transport has been largely phenomenological, with little guidance from electrotransport theory.…”

Section: Introductionmentioning

confidence: 99%

Size and Charge Dependence of Ion Transport in Human Nail Plate

Baswan

LaCount

et al. 2016

Journal of Pharmaceutical Sciences

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The electrical properties of human nail plate are poorly characterized, yet are a key determinate of the potential to treat nail diseases such as onychomycosis using iontophoresis. In order to address this deficiency, molar conductivities of 17 electrolytes comprising 12 ionic species were determined in hydrated human nail plate in vitro. Cation transport numbers across the nail for 11 of these electrolytes were determined by the electromotive force method. Effective ionic mobilities and diffusivities at infinite dilution for all ionic species were determined by regression analysis. The ratios of diffusivities in nail to those in solution were found to correlate inversely with the hydrodynamic radii of the ions according to a power law relationship having an exponent of −1.75 ± 0.27, a substantially steeper size dependence than observed for similar experiments in skin. Effective diffusivities of cations in nail were three-fold higher than those of comparably sized anions. These results reflect the strong size and charge selectivity of the nail plate for ionic conduction and diffusion. The analysis implies that efficient transungual iontophoretic delivery of ionized drugs having radii upwards of 5 Å (approximately MW ≥ 340 Da) will require chemical or mechanical alteration of the nail plate.

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Science of the Nail Apparatus

Berker

Baran

2012

Baran &Amp; Dawber's Diseases of the Nails and Their Management

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Iontophoretic Drug Delivery across Human Nail

Cited by 84 publications

References 22 publications

The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

Size and Charge Dependence of Ion Transport in Human Nail Plate

Science of the Nail Apparatus

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