Drug Permeation through the Three Layers of the Human Nail Plate

Kobayashi, Yoichi; Miyamoto, Masahide; Sugibayashi, Kenji; Morimoto, Yasunori

doi:10.1211/0022357991772448

Cited by 117 publications

(99 citation statements)

References 18 publications

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“…The movement of CPO molecules (in solution) along the length of the suspended nail is also speculated to be due to the orientation of the keratin fibers in a single plane and the hydrophilic nature of the nail. The intermediate layer is the thickest and softest layer of nail plate (27,28). In the intermediate layer, the keratin fibers are arranged in a single plane, parallel to the free end of the nail (29).…”

Section: Discussionmentioning

confidence: 99%

Lateral Drug Diffusion in Human Nails

et al. 2014

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Abstract. The main objective of the current work is to demonstrate the process of passive lateral diffusion in the human nail plate and its effect on the passive transungual permeation of antifungal drug ciclopirox olamine (CPO). A water soluble dye, methyl red sodium salt (MR) was used to visualize the process of lateral diffusion using a novel suspended nail experiment. The decline in concentration of CPO correlates with that of concentration of MR from the proximal to the distal end of the nail in suspended nail study. Three toenails each were trimmed to 5 mm×5 mm (25 mm 2 ), 7 mm×7 mm (49 mm 2 ), and 9 mm×9 mm (81 mm 2 ) to study the extent and effect of lateral diffusion of the CPO on its in vitro transungual permeation. The permeation flux of CPO decreased as the surface area of the toenail increased. There was a positive correlation between the concentrations of CPO and MR in the area of application and in the peripheral area of the toenails of the three surface areas, confirming the findings in the suspended nail experiment. Profound lateral diffusion of CPO was demonstrated and shown to reduce the in vitro passive transungual drug permeation and prolong the lag-time in human toenails. The study data implies that during passive in vitro transungual permeation experiments, the peripheral nail around the area of drug application has to be kept to a minimum, in order to get reliable data which mimics the in vivo situation.

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Section: Discussionmentioning

confidence: 99%

Lateral Drug Diffusion in Human Nails

et al. 2014

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“…Some reports suggest that the nail has properties like those of a hydrophilic gel membrane (13,16), which prevents the penetration of the nail plate by chemicals and drugs (5). In addition, the histopathological examination of nail biopsy specimens revealed the presence of fungi near the distal and proximal nail bed in the distal subungual type (DSO) (11).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Novel Model of Onychomycosis in Rabbits for Evaluation of Antifungal Agents

Shimamura

Kubota

Nagasaka

et al. 2011

Antimicrob Agents Chemother

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We developed a novel model of onychomycosis in which we observed fungi in the deep layer of the nail, and we used the model to evaluate the efficacy of two topical antifungal drugs. To establish an experimental, in vivo model of onychomycosis, we applied Trichophyton mentagrophytes TIMM2789 to the nails of the hind limbs of rabbits that underwent steroid treatment. The nails were taken from the rabbits' feet at 0, 2, and 6 weeks after a 2-week infection. The localization of the fungi was evaluated histopathologically. Some fungi were seen to penetrate to the nail bed, and the infection rate in the sample at 0, 2, and 6 weeks after infection was 57, 87, and 93%, respectively. In addition, fungi proliferated and moved proximally into the nail plate in a manner that depended on the duration of infection. Second, using this model we evaluated antifungal efficacy both by the culture recovery method and histopathological examination. Two topical antifungal drugs, 8% ciclopirox nail lacquer and 5% amorolfine nail lacquer, were applied to the nail for 4 weeks in each group. On histopathological examination, two antifungal treatment groups showed no significant difference against the nontreated control group. However, there were a significantly low fungus-positive rate and intensity of the recovery of fungi on culture between antifungal treatment and nontreated control groups. We therefore suggest that we have established an in vivo model of onychomycosis that is useful for the evaluation of the efficacy of antifungal agents.

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“…These sulfhydryl compounds were shown to be effective transungual enhancers when formulated in aqueous as well as in lipophilic vehicles (Kobayashi et al, 1998(Kobayashi et al, , 1999. TGA, a sulfhydrl compound, is used in the industry to break the disulfide bonds in the hair cortex (Kuzuhara and Hori, 2003).…”

Section: Chemical Enhancersmentioning

confidence: 99%

Chemical method to enhance transungual transport and iontophoresis efficiency

Hao

Smith

2008

International Journal of Pharmaceutics

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Transungual transport is hindered by the inherent small effective pore size of the nail even when it is fully hydrated. The objectives of this study were to determine the effects of chemical enhancers thioglycolic acid (TGA), glycolic acid (GA), and urea (UR) on transungual transport and iontophoresis efficiency. In vitro passive and iontophoretic transport experiments of model permeants mannitol (MA), UR, and tetraethylammonium (TEA) ion across the fully hydrated, enhancer-treated and untreated human nail plates were performed in phosphate-buffered saline. The transport experiments consisted of several stages, alternating between passive and anodal iontophoretic transport at 0.1 mA. Nail water uptake experiments were conducted to determine the water content of the enhancer-treated nails. The effects of the enhancers on transungual electroosmosis were also evaluated. Nails treated with GA and UR did not show any transport enhancement. Treatment with TGA at 0.5 M enhanced passive and iontophoretic transungual transport of MA, UR, and TEA. Increasing the TGA concentration to 1.8 M did not further increase TEA iontophoresis efficiency. The effect of TGA on the nail plates was irreversible. The present study shows the possibility of using a chemical enhancer to reduce transport hindrance in the nail plate and thus enhance passive and iontophoretic transungual transport.

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Drug Permeation through the Three Layers of the Human Nail Plate

Cited by 117 publications

References 18 publications

Lateral Drug Diffusion in Human Nails

Lateral Drug Diffusion in Human Nails

Establishment of a Novel Model of Onychomycosis in Rabbits for Evaluation of Antifungal Agents

Chemical method to enhance transungual transport and iontophoresis efficiency

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