TY - ABST

T1 - Visualization of penetration of topical antifungal drug substances through mycosis-infected nails by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI)

AU - Joly-Tonetti, Nicolas

AU - Pinto, Fernanda Endringer

AU - Bagger, Charlotte

AU - Osman-Ponchet, Hanan

AU - Janfelt, Christian

PY - 2021

Y1 - 2021

N2 - Introduction: Matrix-assisted laser desorption ionization 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 visualize penetration and distribution profile through different tissues but has never been used with nail tissue, especially when infected with onychomycosis. This study used MALDI-MSI technology to visualize 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.Materials and 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 μm, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analyzed by MALDI-MSI.Results: All antifungal actives have been visualized in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localized 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 - Introduction: Matrix-assisted laser desorption ionization 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 visualize penetration and distribution profile through different tissues but has never been used with nail tissue, especially when infected with onychomycosis. This study used MALDI-MSI technology to visualize 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.Materials and 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 μm, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analyzed by MALDI-MSI.Results: All antifungal actives have been visualized in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localized 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.

U2 - /10.1016/j.jaad.2021.06.778

DO - /10.1016/j.jaad.2021.06.778

M3 - Conference abstract in journal

VL - 85

SP - AB191-AB191

JO - American Academy of Dermatology. Journal

JF - American Academy of Dermatology. Journal

SN - 0190-9622

IS - 3

T2 - Virtual Meeting Experience (VMX) of the American-Academy-of-Dermatology (AAD)

Y2 - 23 April 2021 through 25 April 2021

ER -