Effects of Organic Solvents on the Barrier Properties of Human Nail

Smith, Kelly A.; Hao, Jinsong; Li, S. Kevin

doi:10.1002/jps.22590

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…This relatively rapid uptake of water into the nail has been inferred from previous investigations (14,15) but the transport process has never been visualized before in such a direct fashion. The results are consistent with the nail being characterized as a dense hydrogel containing overlapping keratin fibers, which create small, tortuous, pore pathways that favor the permeability of small, hydrophilic molecules, such as water (16).…”

Section: Significancesupporting

confidence: 76%

“…Notably, and self-evidently, the rate of diffusion of PG and DMSO is substantially less than that of D 2 O (which had permeated 100 μm in only ∼30 min), the molecular size of which is about one-quarter of that of the two other solvents: the molecular weights of water, PG and DMSO are 18.0, 76.1, and 78.1, respectively; the corresponding molar volumes are 18.0, 73.4, and 71.0 cm 3 . The relatively poorer uptake of PG and DMSO into the nail has been reported (16,17) and their penetration-enhancing abilities are less than clear cut (18). Rotating 3D composite images showing the progressive penetration of PG-d 8 and DMSO-d 6 into the nail are presented in Movies S2 and S3, respectively.…”

Section: Significancementioning

confidence: 99%

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Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

Chiu

Belsey

Garrett

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D2O), propylene glycol (PG-d8), and dimethyl sulphoxide (DMSO-d6) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D2O, PG-d8/DMSO-d6, and the nail through the O-D, -CD2, and -CH2 bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D2O was more than an order of magnitude faster than that of PG-d8 and DMSO-d6. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease.

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Section: Significancesupporting

confidence: 76%

Section: Significancementioning

confidence: 99%

Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

Chiu

Belsey

Garrett

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Smith et al [48] compared the effect of plain organic and binary mixture of aqueous organic solvent systems on nail hydration and permeability. Ungual uptake and transport was correlated to the concentration of organic solvent employed in the study.…”

Section: Ungual Permeation Enhancersmentioning

confidence: 99%

Transungual permeation: current insights

Bhuptani

Deshpande

Patravale

2015

Drug Deliv. and Transl. Res.

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Nail disorders are beyond cosmetic concern; besides discomfort in the performance of daily chores, they disturb patients psychologically and affect their quality of life. Fungal nail infection (onychomycosis) is the most prevalent nail-related disorder affecting a major population worldwide. Overcoming the impenetrable nail barrier is the toughest challenge for the development of efficacious topical ungual formulation. Sophisticated techniques such as iontophoresis and photodynamic therapy have been proven to improve transungual permeation. This article provides an updated and concise discussion regarding the conventional approach and upcoming novel approaches focused to alter the nail barrier. A comprehensive description regarding preformulation screening techniques for the identification of potential ungual enhancers is also described in this review while highlighting the current pitfalls for the development of ungual delivery.

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“…Any increase in drug solubility engendered by adding an organic solvent to a formulation to improve transungual drug delivery may be counteracted by the reduction in nail hydration and permeability caused by the solvent itself. Smith et al ( 24 ) studied the effect of organic solvents EtOH, PPG, and PEG on the barrier properties of nail by demonstrating that permeant partitioning into and transport across the nail were shown to decrease as the concentration of the organic solvent in the binary solvent system increased.…”

Section: Table IIImentioning

confidence: 99%

Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin

et al. 2018

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To promote transungual permeation of nystatin (NYST), molecule with high molecular weight, no water-soluble, amphoteric by iontophoresis. The synergic effect of the combination of cetylpyridinium chloride, CPC, or polyoxyethylene (20) sorbitan monooleate, TW80, and iontophoresis was investigated. In vitro permeation experiments were carried out through bovine hoof slices using vertical diffusion cells. A low current density (0.2 mA/cm) was applied by introducing Ag/AgCl electrodes in the donor (anode) and receptor (cathode) chambers. The donor phase consisted of a solution, a suspension, or gel-type vehicles containing NYST and surfactants in pH 5.6 HEPES buffer. The addition of CPC to NYST suspension (SOSP) produced a fivefold increase on the permeability of the bovine hoof membrane to the drug. The application of anodal iontophoresis further improved NYST flux. Conversely, NYST transungual permeation was not influenced by TW80 either in the passive diffusion or iontophoretic flux. Furthermore, the iontophoretic treatment does not appear to induce irreversible alterations to the hoof bovine membranes. The present work demonstrated the efficacy of iontophoresis as a treatment for different nail pathologies with large molecules very slightly soluble in water without irreversibly affecting the nail structure. A synergistic effect between CPC and iontophoresis was observed.

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Effects of Organic Solvents on the Barrier Properties of Human Nail

Cited by 22 publications

References 22 publications

Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

Transungual permeation: current insights

Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin

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