Is the Fractional Laser Still Effective in Assisting Cutaneous Macromolecule Delivery in Barrier-Deficient Skin? Psoriasis and Atopic Dermatitis as the Disease Models

Lee, William R.; Shen, Shing Chuan; Sung, Ching-Hwa; Liu, Pei Ying; Fang, Jia You

doi:10.1007/s11095-018-2413-6

Cited by 9 publications

(3 citation statements)

References 51 publications

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“…Since the concept of LAUD is to physically disrupt and thereby overcome barriers to topical drug delivery, our results show that AFL‐pretreatment of healthy nail tissue leads to a larger increase in permeation than in already impaired fungal nail samples. This finding is in line with the results from a study on laser‐assisted drug delivery in atopic dermatitis, demonstrating that barrier‐deficient skin benefits from microporation though to a lesser degree than intact skin 51 . Other types of nail disorders, such as psoriatic nail disease, may present with similar clinical features but exhibit different micromorphologic changes and lower increase in porosity which could make them better targets for LAUD 52,53 .…”

Section: Discussionsupporting

confidence: 84%

“…This finding is in line with the results from a study on laser-assisted drug delivery in atopic dermatitis, demonstrating that barrier-deficient skin benefits from microporation though to a lesser degree than intact skin. 51 Other types of nail disorders, such as psoriatic nail disease, may present with similar clinical features but exhibit different micromorphologic changes and lower increase in porosity which could make them better targets for LAUD. 52,53 Since previous preclinical LAUD studies used healthy instead of diseased nail tissue, their results should be interpreted with caution as pretreatment effects for delivery enhancement may be overestimated.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2022

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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

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Fractional modality creates microscopic vertical channels on the cutaneous surface with unaffected viable tissue surrounding the microchannels. The ablated area can be recovered within 1 day 9 . Fractional laser treatment may be feasible for siRNA absorption, as it offers a strategy for delivering the polar macromolecules through the lipid-rich SC to a specific region and cellular population.…”

Section: Introductionmentioning

confidence: 99%

Fractional Laser-Mediated siRNA Delivery for Mitigating Psoriasis-like Lesions via IL-6 Silencing

Lee

Lin

Alalaiwe

et al. 2020

Molecular Therapy - Nucleic Acids

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The poor permeability of topically applied macromolecules such as small interfering RNA (siRNA) has inhibited the translation to clinical application. In this study, the fractional CO2 laser-assisted approach was developed to describe siRNA permeation enhancement mediated by the created microchannels for silencing the gene to treat psoriasiform lesions. In vitro permeation using Franz cell and in vivo interleukin (IL)-6 silencing using psoriasis-like plaque in mice were evaluated to verify the impact of the laser irradiation. Low-fluence laser exposure enabled a significant increase in skin transport of siRNA, peptide, and 5-fluorouracil (5-FU). The laser treatment resulted in the enhancement of siRNA flux by 33- and 14-fold as compared to the control in nude mouse and pig skin, respectively. The laser exposure also promoted siRNA penetration across psoriatic and photoaging skins with the deficient barrier, although the enhancement level was minor compared to that of intact skin. The 3D images of confocal microscopy revealed a diffusion of macromolecules into the laser-created microchannels; the radial and vertical distribution to the surrounding and deep tissues followed this. A single laser treatment and the following topical siRNA administration were able to reduce IL-6 expression by 64% in the psoriatic skin model. Laser assistance led to the marked improvement in the plaque and the reduction of specific cytokine expression, keratinocyte proliferation, and neutrophil infiltration. Our data support the use of the fractional laser for delivery of functional nucleic acid into the skin and the target cells.

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Fundamentals of fractional laser-assisted drug delivery: An in-depth guide to experimental methodology and data interpretation

Wenande

Anderson

Hædersdal

2020

Advanced Drug Delivery Reviews

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Is the Fractional Laser Still Effective in Assisting Cutaneous Macromolecule Delivery in Barrier-Deficient Skin? Psoriasis and Atopic Dermatitis as the Disease Models

Abstract: The fractional laser was valid for ameliorating macromolecule permeation into barrier-disrupted skin although the enhancement level was lower than that of normal skin.

Cited by 9 publications

References 51 publications

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

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

Fractional Laser-Mediated siRNA Delivery for Mitigating Psoriasis-like Lesions via IL-6 Silencing

Fundamentals of fractional laser-assisted drug delivery: An in-depth guide to experimental methodology and data interpretation

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Is the Fractional Laser Still Effective in Assisting Cutaneous Macromolecule Delivery in Barrier-Deficient Skin? Psoriasis and Atopic Dermatitis as the Disease Models

Abstract: The fractional laser was valid for ameliorating macromolecule permeation into barrier-disrupted skin although the enhancement level was lower than that of normal skin.

Cited by 9 publications

References 51 publications

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

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

Fractional Laser-Mediated siRNA Delivery for Mitigating Psoriasis-like Lesions via IL-6 Silencing

Fundamentals of fractional laser-assisted drug delivery: An in-depth guide to experimental methodology and data interpretation

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Product

Resources

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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

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