Human nail plate modifications induced by onychomycosis: implications for topical therapy.

A Baraldi,S Murdan,M J Traynor,S Guesné,S A Jones,M B Brown,W J Mcauley

doi:10.1007/s11095-014-1562-5

A Baraldi, S Murdan + Show 5 more

Open Access

https://doi.org/10.1007/s11095-014-1562-5

Copy DOI

Abstract

PurposeThrough the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.MethodsThe mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake.ResultsChronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm3; diseased 1.29 ± 0.00 g/cm3). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle.ConclusionsOnchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-014-1562-5) contains supplementary material, which is available to authorized users.

Highlights

Onychomycosis refers to the infection of the nail unit by fungi
All nail comparisons were matched throughout the study i.e., finger nails were compared with finger nails and toe nails were compared to toe nails, the source of the nail was noted in the text only when it was relevant to the data interpretation
The thickness of healthy nails collected in this study was found to be between 0.3–1 mm which agrees with previous reports [30]

Summary

Introduction

Onychomycosis refers to the infection of the nail unit by fungi. It constitutes 40% of all reported nail disorders [1]. Topical medication appears to provide relatively low cure rates (typically up to 30%) and relatively long treatment times (12 months or longer) [3]. One reason for the low cure rates of topical therapy is thought to be the inability of active agents to penetrate the nail plate, but the studies that propose this generally use healthy tissue to study chemical penetration and there remains a need to conduct such studies in the presence of the disease [4,5,6]

Objectives

Methods

Results