Visualisation of penetration of topical antifungal drug substances through mycosis-infected nails by matrix-assisted laser desorption ionisation mass spectrometry imaging
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Visualisation of penetration of topical antifungal drug substances through mycosis-infected nails by matrix-assisted laser desorption ionisation mass spectrometry imaging. / Endringer Pinto, Fernanda; Bagger, Charlotte; Kunze, Gernot; Joly-Tonetti, Nicolas; Thenot, Jean-Paul; Osman-Ponchet, Hanan; Janfelt, Christian.
In: Mycoses, Vol. 63, No. 8, 2020, p. 869-875.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Visualisation of penetration of topical antifungal drug substances through mycosis-infected nails by matrix-assisted laser desorption ionisation mass spectrometry imaging
AU - Endringer Pinto, Fernanda
AU - Bagger, Charlotte
AU - Kunze, Gernot
AU - Joly-Tonetti, Nicolas
AU - Thenot, Jean-Paul
AU - Osman-Ponchet, Hanan
AU - Janfelt, Christian
PY - 2020
Y1 - 2020
N2 - Background Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) is a mass spectrometry-based technique, which can be applied for compound-specific imaging of pharmaceuticals in tissues samples. MALDI-MSI technology is widely used to visualise penetration and distribution profile through different tissues but has never been used with nail tissue.Objectives This study used MALDI-MSI technology to visualise distribution profile and penetration into ex vivo human mycosis-infected toenails of three antifungal active ingredients amorolfine, ciclopirox and naftifine contained in topical onychomycosis nail treatment preparations, marketed as Loceryl(R), Ciclopoli(R) and Exoderil(R).Methods Three mycosis-infected toenails were used for each treatment condition. Six and twenty-four hours after one single topical application of antifungal drugs, excess of formulation was removed, nails were cryo-sectioned at a thickness of 20 mu m, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analysed by MALDI-MSI.Results All antifungal actives have been visualised in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localised distribution in the uppermost layer of the nail plate. In comparison, amorolfine diffuses through the nail plate to the deep layers already 6 hours after application and keeps diffusing towards the lowest nail layers within 24 hours.Conclusions This study shows for the first-time distribution and penetration of certain antifungal actives into human nails using MALDI-MSI analysis. The results showed a more homogeneous distribution of amorolfine to nail and a better penetration through the infected nails than ciclopirox and naftifine.
AB - Background Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) is a mass spectrometry-based technique, which can be applied for compound-specific imaging of pharmaceuticals in tissues samples. MALDI-MSI technology is widely used to visualise penetration and distribution profile through different tissues but has never been used with nail tissue.Objectives This study used MALDI-MSI technology to visualise distribution profile and penetration into ex vivo human mycosis-infected toenails of three antifungal active ingredients amorolfine, ciclopirox and naftifine contained in topical onychomycosis nail treatment preparations, marketed as Loceryl(R), Ciclopoli(R) and Exoderil(R).Methods Three mycosis-infected toenails were used for each treatment condition. Six and twenty-four hours after one single topical application of antifungal drugs, excess of formulation was removed, nails were cryo-sectioned at a thickness of 20 mu m, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analysed by MALDI-MSI.Results All antifungal actives have been visualised in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localised distribution in the uppermost layer of the nail plate. In comparison, amorolfine diffuses through the nail plate to the deep layers already 6 hours after application and keeps diffusing towards the lowest nail layers within 24 hours.Conclusions This study shows for the first-time distribution and penetration of certain antifungal actives into human nails using MALDI-MSI analysis. The results showed a more homogeneous distribution of amorolfine to nail and a better penetration through the infected nails than ciclopirox and naftifine.
KW - amorolfine 5% nail lacquer
KW - antifungal efficacy
KW - ex vivo
KW - MALDI-MSI
KW - nail penetration
KW - topical antifungals
KW - NAFTIFINE
KW - PERMEATION
KW - DELIVERY
KW - BARRIER
U2 - 10.1111/myc.13103
DO - 10.1111/myc.13103
M3 - Journal article
C2 - 32406142
VL - 63
SP - 869
EP - 875
JO - Mycoses
JF - Mycoses
SN - 0933-7407
IS - 8
ER -
ID: 247075479