Dataset Information

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

ABSTRACT:

Purpose

Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.

Methods

The 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.

Results

Chronic 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/cm(3); diseased 1.29 ± 0.00 g/cm(3)). 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.

Conclusions

Onchomycotic 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.

SUBMITTER: Baraldi A

PROVIDER: S-EPMC4381097 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionOnychomycosis is a fungal nail infection, frequently caused by dermatophytes, which occurs in 2-14% of Western adults. The present study was set up to evaluate the efficacy and safety of a water-based, peelable nail polish (daily application), which acidifies the nail environment, versus a 5% amorolfine nail lacquer (weekly application) for topical treatment of mild-to-moderate onychomycosis.MethodsOne hundred two adults were randomized in this open, prospective, blinded trial. Clinical efficacy was evaluated at baseline and days 30, 60, 120, and 180, respectively. All patients underwent microbiological testing (at baseline and study end). The primary objective of this trial was the change in the percentage of healthy nail surface at day 180.ResultsThe percentage of healthy surface between baseline and day 180 increased with 11.8% in the test product group and 13.2% in the amorolfine group, which were statistically comparable. Other onychomycosis-related parameters (dystrophy, discolouration, thickening, and healthy aspect, respectively) showed significant (p < 0.05) improvement after 180 days (versus baseline) with both treatments. Clinical performance was further confirmed by the frequency of patients showing onychomycosis improvement or success at the end of the study: 96.0% (test product) versus 79.6% (amorolfine). Microbiological results and improved quality of life confirmed clinical performance. Both treatments were well tolerated and appreciated for their properties and efficacy.ConclusionThe present trial confirmed the clinical performance of daily acidification of the nail, as reflected by (1) a comparable increase of percentage of healthy nail surface following treatment with the test product versus amorolfine, (2) the overall improvement of other onychomycosis-related parameters, (3) user convenience, and (4) absence of side effects. These data indicate that daily application of an aqueous, acetic acid-based, peelable solution can be a convenient, safe, and equally effective alternative for the topical management of onychomycosis.Trial registrationClinicalTrials.gov identifier; NCT03382717 FUNDING: Oystershell Laboratories.

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