TY - JOUR

T1 - Fractional CO2 laser ablation leads to enhanced permeation of a fluorescent dye in healthy and mycotic nails-An imaging investigation of laser-tissue effects and their impact on ungual drug delivery

AU - Ortner, Vinzent Kevin

AU - Nguyen, Nhi

AU - Brewer, Jonathan R.

AU - Solovyeva, Vita

AU - Haedersdal, Merete

AU - Philipsen, Peter Alshede

PY - 2022/8

Y1 - 2022/8

N2 - Purpose Conventional oral antifungal therapies for onychomycosis (OM) often do not achieve complete cure and may be associated with adverse effects, medical interactions, and compliance issues restricting their use in a large group of patients. The topical treatment provides an alternative to bypass the systemic side effects but is limited by the physical barrier of the nail plate. Ablative fractional laser (AFL) treatment can be used to improve the penetration of topical drugs into the nail. This study visualized the effects of laser ablation on nail tissue and assessed their impact on the biodistribution of a fluorescent dye in healthy and fungal nail tissue. Methods For the qualitative assessment of CO2 AFL effects on healthy nail tissue, scanning electron microscopy (SEM), coherent anti-Stokes Raman scattering microscopy (CARS-M), and widefield fluorescence microscopy (WFM) were used. To quantitate the effect of laser-pretreatment on the delivery of a fluorescent dye, ATTO-647N, into healthy and fungal nail tissue, ablation depth, nail plate thickness, and ATTO-647N fluorescence intensity in three nail plate layers were measured using WFM. A total of 30 nail clippings (healthy n = 18, fungal n = 12) were collected. An aqueous ATTO-647N solution was directly applied to the dorsal surface of 24 nail samples (healthy n = 12, fungal n = 12) and incubated for 4 hours, of which half (healthy n = 6, fungal n = 6) had been pretreated with AFL (30 mJ/mb, 15% density, 300 Hz, pulse duration

AB - Purpose Conventional oral antifungal therapies for onychomycosis (OM) often do not achieve complete cure and may be associated with adverse effects, medical interactions, and compliance issues restricting their use in a large group of patients. The topical treatment provides an alternative to bypass the systemic side effects but is limited by the physical barrier of the nail plate. Ablative fractional laser (AFL) treatment can be used to improve the penetration of topical drugs into the nail. This study visualized the effects of laser ablation on nail tissue and assessed their impact on the biodistribution of a fluorescent dye in healthy and fungal nail tissue. Methods For the qualitative assessment of CO2 AFL effects on healthy nail tissue, scanning electron microscopy (SEM), coherent anti-Stokes Raman scattering microscopy (CARS-M), and widefield fluorescence microscopy (WFM) were used. To quantitate the effect of laser-pretreatment on the delivery of a fluorescent dye, ATTO-647N, into healthy and fungal nail tissue, ablation depth, nail plate thickness, and ATTO-647N fluorescence intensity in three nail plate layers were measured using WFM. A total of 30 nail clippings (healthy n = 18, fungal n = 12) were collected. An aqueous ATTO-647N solution was directly applied to the dorsal surface of 24 nail samples (healthy n = 12, fungal n = 12) and incubated for 4 hours, of which half (healthy n = 6, fungal n = 6) had been pretreated with AFL (30 mJ/mb, 15% density, 300 Hz, pulse duration

KW - fluorescence microscopy

KW - fractional CO2 laser

KW - laser-assisted drug delivery

KW - nail fungus

KW - onychomycosis

KW - CARBON-DIOXIDE LASER

KW - QUALITY-OF-LIFE

KW - TOENAIL ONYCHOMYCOSIS

KW - PHOTODYNAMIC THERAPY

KW - AMOROLFINE LACQUER

KW - PENETRATION

KW - PORATION

U2 - 10.1002/lsm.23541

DO - 10.1002/lsm.23541

M3 - Journal article

C2 - 35451510

VL - 54

SP - 861

EP - 874

JO - Lasers in Surgery and Medicine

JF - Lasers in Surgery and Medicine

SN - 0196-8092

IS - 6

ER -