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Journal ArticleDOI

A few aspects of transonychial water loss (TOWL): inter-individual, and intra-individual inter-finger, inter-hand and inter-day variabilities, and the influence of nail plate hydration, filing and varnish.

01 Oct 2008-European Journal of Pharmaceutics and Biopharmaceutics (Elsevier)-Vol. 70, Iss: 2, pp 684-689
TL;DR: Nail varnish application reduced transonychial water loss; the different extent of TOWL reduction by different varnishes suggests a potential use of TowL measurements for product comparisons.
About: This article is published in European Journal of Pharmaceutics and Biopharmaceutics.The article was published on 2008-10-01 and is currently open access. It has received 35 citations till now.

Summary (2 min read)

INTRODUCTION

  • Transepidermal water loss (TEWL) – insensible water loss from the body through the skin to the outside environment - is a widely employed parameter to characterize the barrier function of human skin.
  • Jemec et al. (3), Kronauer et al. (4) and Kruger et al. (5) used an open chamber evaporimeter while Nuutinen et al. (7) used a closed chamber VapoMeter.
  • Zaun (6) raised the problems of ensuring contact between the probe and the rigid nail plate and questioned the accuracy of TOWL measurements, given that the probe used was designed to measure water loss from the elastic skin.
  • The aim of the work described in this paper was to conduct a systematic investigation of TOWL, using a specially designed measurement cap for the nail plate, to identify the variables which affect TOWL and to identify possible uses of TOWL measurements.
  • Research into the topical treatment of nail diseases is on the increase (8), and it is expected that TOWL measurements will be an additional tool in the ungual diagnostic and drug delivery fields.

Materials

  • The condenser-chamber AquaFlux (Biox, UK) was used to measure TOWL.
  • It consists of a short stainless steel tube fitted with a rubber O-ring for sealing against the nail plate.
  • The tube internal diameter was 3.8mm and the instrumental flux density calibration was adjusted in the software via a Biox-supplied correction factor of 0.542.
  • The cosmetic nail varnish formulations, Snowdrop No 17 Lasting Fix and Teflon ® Tuff TM were obtained from Boots Chemists, U.K., and from Superdrug stores plc, U.K., respectively.
  • Penlac ® (the original 8% ciclopirox nail lacquer by Aventis Pharma Deutschland GmnH) was a gift from York Pharma (UK).

Methods

  • TOWL measurement TOWL of healthy finger and toenails of 3 individuals were measured.
  • To determine the influence of nail plate thickness on TOWL, the latter for all fingernails was measured on the same day and thickness of freshly cut nail clippings was measured using an electronic micrometer.
  • To determine the influence of filing on TOWL, the nail plate surface was filed using cosmetic or pharmaceutical files.
  • Influence of nail varnish application and removal on TOWL, and comparison between nail products.

Inter-individual variability in TOWL

  • A broad range of TOWL values was recorded; 28-75 g/m 2 h for fingernails and 26-48 g/m 2 h for toenails and significant differences in TOWL among individuals were observed .
  • This was expected, given the obvious inter-individual variabilities in the nail plate properties, such as nail plate thickness.
  • The chemical composition of nail plates, such as water and lipid content, are also likely to differ among individuals, which would influence TOWL values.
  • Inter-individual variability in TOWL was found to be much greater than intra-individual variability for both finger and toenails .
  • The differences in TOWL can be partially assigned to the different thicknesses of the nail plates, as shown in Figure 2, where a relatively good correlation between thickness and TOWL was found (Pearson correlations were found to be -0.83 and -0.92 for Individuals 1&2).

Inter-hand/foot variability in TOWL

  • TOWL values for the same digits of the opposite hands of the same individual were found to be different, though the difference was not very large .
  • When TOWL for the same finger/toe nail (in the same individual) was measured on different days, TOWL was found to vary to a small extent.
  • When the relative humidity and TOWL over the 8 days were plotted together , the relative humidity profile reflected the TOWL profiles to a certain extent, and Pearson correlation values of 0.5-0.6 were found.
  • The longer the duration of fingernail immersion in water, the greater amount of water was absorbed by the nail plate and subsequently released, i.e. the greater the TOWL, until a saturation point was reached after a 5minute immersion in water.
  • The profiles in Figure 7 show that TOWL measurements could be used to compare nail varnish preparations for their ability to reduce TOWL, and thereby compare their ability to increase nail plate hydration and drug permeation, at least in initial studies, if the hypothesis above is proven.

CONCLUSIONS

  • A wide range of TOWL values was found, which correlated to a certain extent with the literature.
  • The significant inter-individual variability observed indicates the difficulties when TOWL values are averaged for comparison purposes.
  • The lower intra-individual variability observed suggests that using an individual’s own nails as controls, e.g. when investigating the influence of disease, might be more appropriate.
  • The rapid response in TOWL upon nail wetting warns that the subject should avoid nail wetting for a suitable period before TOWL measurements.
  • As expected, filing increased TOWL considerably while varnish application reduced TOWL.

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Citations
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Journal ArticleDOI
TL;DR: The topical therapy of nail diseases, especially of onychomycosis, and to a smaller extent, of nail psoriasis, is desirable to avoid the side effects associated with their systemic therapy, to increase patient compliance and reduce the cost of treatment.
Abstract: The topical therapy of nail diseases, especially of onychomycosis, and to a smaller extent, of nail psoriasis, is desirable to avoid the side effects associated with their systemic therapy, to increase patient compliance and reduce the cost of treatment. Systemic therapy is however the mainstay of treatment due to the poor permeability of the nail plate to topically applied drugs. For effective topical therapy, ungual drug permeation must be enhanced. This can be achieved by disrupting the nail plate using physical techniques or chemical agents. Alternatively, drug permeation into the intact nail plate may be encouraged, for example, by iontophoresis or by formulating the drug within a vehicle which enables high drug partition out of the vehicle and into the nail plate. The physical techniques (manual and electrical nail abrasion, acid etching, ablation by lasers, microporation, application of low-frequency ultrasound and electric currents) and chemicals (thiols, sulphites, hydrogen peroxide, urea, water, enzymes) that have shown ungual enhancer activity are discussed in this review. Optimal drug formulation, while crucial to ungual drug delivery, is only briefly reviewed due to the limited literature.

138 citations


Cites background from "A few aspects of transonychial wate..."

  • ...Lacquers also reduce trans-onycheal water loss [94,95] , which could lead to increased hydration of the nail plate [94] , which could in turn increase drug diffusivity in the nail [96] ....

    [...]

Journal ArticleDOI
18 Jan 2017-Mycoses
TL;DR: The current understanding of the nail microstructure, composition and diseases is reviewed and a few of the parameters affecting the nail permeability and potential causes of the recurrence of fungal nail infection are discussed.
Abstract: The topical treatment of nail fungal infections has been a focal point of nail research in the past few decades as it offers a much safer and focused alternative to conventional oral therapy. Although the current focus remains on exploring the ways of enhancing permeation through the formidable nail barrier, the understanding of the nail microstructure and composition is far from complete. This article reviews our current understanding of the nail microstructure, composition and diseases. A few of the parameters affecting the nail permeability and potential causes of the recurrence of fungal nail infection are also discussed.

69 citations

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TL;DR: To identify permeation enhancers and to improve the understanding of physicochemical parameters that influence drug permeation, cadaver nails in modified Franz-type diffusion cells were employed and hydrophobins were suggested to be efficient in drug delivery through the nail plate.

65 citations

Journal ArticleDOI
TL;DR: The current knowledge and recent advances in the field of transungual drug delivery are reviewed and guidance on development of topical/ungual therapeutics for management of nail diseases is provided, with special emphasis on management of onychomycosis, the most common nail disease.

58 citations

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TL;DR: Iontophoresis was able to deliver an effective amount of CIC into and across the nails, and this suggests the feasibility of a constant voltage battery-powered transungual iontophoretic device.

42 citations

References
More filters
Journal ArticleDOI
TL;DR: Despite different morphological characteristics, it appears that hair and nail have differentiated along very similar lines, however, subtle differences in the relative proportion and composition of the structural proteins can be detected.

127 citations


"A few aspects of transonychial wate..." refers background in this paper

  • ...A direct relationship between relative humidity and nail water content has been reported in vitro and to a much smaller extent, in vivo (12-15)....

    [...]

Journal ArticleDOI
TL;DR: The in‐vitro permeation characteristics of a water soluble model drug, 5‐fluorouracil, and a poorly water solublemodel drug, flurbiprofen, were investigated through three layers of the human nail plate, using a modified side‐by‐side diffusion cell.
Abstract: The in-vitro permeation characteristics of a water soluble model drug, 5-fluorouracil, and a poorly water soluble model drug, flurbiprofen, were investigated through three layers of the human nail plate (namely, the dorsal, intermediate and ventral nail plates), using a modified side-by-side diffusion cell. The dorsal-filed nail plate, the ventral-filed nail plate and the dorsal-and-ventral-filed nail plate were prepared to known thicknesses and then used with the full-thickness nail plate to investigate the permeation characteristics of each single layer. Most of the lipids in the human nail plate were found in the dorsal and ventral layers. The rank orders of the permeation fluxes for 5-fluorouracil and flurbiprofen were both: dorsal-and-ventral-filed nail plate > dorsal-filed nail plate > ventral-filed nail plate > full-thickness nail plate. With respect to 5-fluorouracil permeation through each single layer, the permeability coefficient of the intermediate layer was higher than those of other single layers. However in the case of flurbiprofen, the permeability coefficient of the ventral layer was higher than other single layers. The diffusion coefficients of 5-fluorouracil and flurbiprofen in the dorsal layer were the lowest of any single layer. The drug concentration in each layer was estimated using each respective permeation parameter. The drug concentration in the nail plate was observed to be dependent on the solubility and the flux of the drug. From these findings, we suggest that the human nail plate behaves like a hydrophilic gel membrane rather than a lipophilic partition membrane and that the upper layer functions as the main nail barrier to drug permeation through its low diffusivity against the drugs.

125 citations


"A few aspects of transonychial wate..." refers background in this paper

  • ...Kobayashi et al (17) found that filing the dorsal nail greatly increased drug flux in vitro and suggested that the dorsal nail surface is the main barrier to drug penetration into the nail plate....

    [...]

  • ...calculated the thickness ratio of each layer to be 3:5:2 for dorsal: intermediate: ventral (17)....

    [...]

  • ...Kobayashi et al. calculated the thickness ratio of each layer to be 3:5:2 for dorsal: intermediate: ventral (17)....

    [...]

  • ...Transonychial Water Loss (TOWL) – water loss from the body through the nail plate into the outside environment – has also been measured, but to a much more limited extent (17), presumably due to the less extensive research in nail diseases and their treatment....

    [...]

Journal ArticleDOI
TL;DR: The impact of hydration on the permeation of the antifungal drug, ketoconazole, through excised human nails in vitro was evaluated in diffusion cell studies as discussed by the authors.

96 citations

Journal ArticleDOI
TL;DR: The 5% nail Lacquer was more effective than the 2% nail lacquer when used once weekly for up to 6 months for the treatment of mild to moderate onychomycosis, and both concentrations were well tolerated.
Abstract: Altogether 157 patients with onychomycosis affecting not more than 80% of the surface area of nail with intact lunula and matrix were treated once weekly for up to 6 months with amorolfine nail lacquer (2 or 5%) in a double-blind randomized design. Clinical examinations were carried out before, monthly during, and 1 and 3 months after therapy. Mycological examinations were performed before, 1 and 3 months after therapy. One hundred patients were evaluated. According to the overall assessment by the investigators, which was based on the clinical response and mycological findings, there was cure in 12%, improvement in 55% and failure in 33+ of the 2% group. The corresponding figures in the 5% group were: cure in 38%, improvement in 32% and failure in 30%. The difference in the number of cures was statistically significant in favour of the 5% nail lacquer. The most common pathogens isolated were Trichophyton rubrum in 59% of cases and Trichophyton mentagrophytes in 22%. Three months after the end of the treatment the mycological culture was negative in 55% of the 2% group and in 60% of the 5% group. Both concentrations were well tolerated. Only three patients (2%) experienced mild local adverse events. No systemic side-effects occurred and no patient discontinued treatment due to an adverse event. In conclusion, the 5% nail lacquer was more effective than the 2% nail lacquer when used once weekly for up to 6 months for the treatment of mild to moderate onychomycosis, and both concentrations were well tolerated.

94 citations


"A few aspects of transonychial wate..." refers background in this paper

  • ...In clinical trials, filing the nail plate surface prior to drug application/re-application was found to be essential for the success of topical treatment (18-19), and patient information leaftlets of the pharmaceutical lacquers,...

    [...]

Journal ArticleDOI
TL;DR: Optical coherence tomography (OCT) is an optical imaging modality which may provide improved data in nail diseases and is of particular interest in the study of nails.
Abstract: Summary Background Nail diseases are often troubling to the patient and may present a diagnostic challenge to the dermatologist. Biopsies from the nail may be required although often perceived uncomfortable by the patient and potentially scarring. Noninvasive technologies are therefore of particular interest in the study of nails. Optical coherence tomography (OCT) is an optical imaging modality which may provide improved data. Objectives This study evaluates nail morphology and thickness in OCT images in comparison with high-frequency ultrasound (HFUS) imaging of the nail. Methods Ten healthy volunteers were recruited for imaging and nail measurements; OCT and HFUS images were compared qualitatively. Nail thickness measurements with four different techniques were compared: ultrasound, OCT, polarization-sensitive (PS) OCT and callipers. The OCT system was developed at Risoe National Laboratory, Denmark. A commercially available 20-MHz ultrasound system (Dermascan; Cortex Technology, Hadsund, Denmark) was used. Results In standard OCT the nail plate appeared as a layered structure containing a varying number of horizontal homogeneous bands of varying intensity and thickness. PS-OCT images of the nail plate also showed a layered structure. The refractive index of the nail was 1·47 ± 0·09. OCT and PS-OCT had low coefficients of variation, 6·31 and 6·53, respectively, compared with other methods: HFUS 12·70 and callipers 14·03. Conclusion PS-OCT has to our knowledge not been applied to OCT analysis of the nail, and offers some advantages in separation of the nail bed from the nail plate.

59 citations

Frequently Asked Questions (1)
Q1. What are the contributions mentioned in the paper "A few aspects of transonychial water loss (towl): inter-individual, and intra- individual inter-finger, inter-hand and inter-day variabilities, and the influence of nail plate hydration, filing and varnish" ?

In this paper, the authors used a specially designed measurement cap for the nail plate, to identify the variables which affect TOWL and to identify possible uses of TEWL measurements.