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

Abstract

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. Topical treatment can 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 of 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 CO 2 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 <1 ms). Results: Imaging revealed a three-layered nail structure, an AFL-induced porous ablation crater, and changes in autofluorescence. While intact fungal samples showed a 106% higher ATTO-647N signal intensity than healthy controls, microporation led to a significantly increased fluorophore permeation in all samples (p < 0.0001). AFL processing of nail tissue enhanced topical delivery of ATTO-647N in all layers, (average increase: healthy +108%, fungal +33%), most pronounced in the top nail layer (healthy +122%, fungal +68%). While proportionally deeper ablation craters correlated moderately with higher fluorescence intensities in healthy nail tissue, fungal samples showed no significant relationship. Conclusion: Fractional CO 2 laser microporation is a simple way of enhancing the passive delivery of topically applied ATTO-647N. Although the impaired nail

Investigating the efficacy and safety of calcipotriol/betamethasone dipropionate foam and laser microporation for psoriatic nail disease—A hybrid trial using a smartphone application, optical coherence tomography, andpatient‐reportedoutcome measures

“…34,35 Commonly referred to as laserassisted drug delivery, this technique has been established in the management of various skin conditions and gradually expanding into onychology. [36][37][38] In the context of PND, two RCTs recently investigated the value of AFL as a delivery enhancement strategy for topical treatment using Cal/BD gel and Tazarotene gel, achieving a change from baseline severity between À34% and À48%, respectively. 3,33 Optical coherence tomography (OCT) is a noninvasive technique that has been used to support clinical assessments of dermatological conditions, including PND.…”

“…An emerging concept in topical treatment of nail disease is the use of ablative fractional laser (AFL) as a pretreatment to boost the uptake of topically applied drugs 34,35 . Commonly referred to as laser‐assisted drug delivery, this technique has been established in the management of various skin conditions and gradually expanding into onychology 36–38 . In the context of PND, two RCTs recently investigated the value of AFL as a delivery enhancement strategy for topical treatment using Cal/BD gel and Tazarotene gel, achieving a change from baseline severity between −34% and −48%, respectively 3,33 …”