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      Mechanism of human nail poration by high-repetition-rate, femtosecond laser ablation

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          Abstract

          Optical poration, or drilling, of the human nail has the potential to drastically improve transungual drug delivery. However, this approach is accompanied by thermal damage to the nail tissue surrounding the laser radiation-created pore. In this paper, fluorescence microscopy has been employed to quantitatively evaluate thermal damage to the nail induced by laser ablation with 80 MHz, nanojoule, femtosecond pulses delivered via a hollow-core fibre. An empirical relation has been established between the intensity of the resulting fluorescence signal and temperature to which the nail was exposed. Using this relationship, detailed temperature maps have been created of the areas surrounding the pores, enabling the mechanism of poration to be better understood. It was deduced that plasma-mediated ablation is primarily responsible for nail tissue ablation at the centre of the pore, while cumulative photothermal processes dominate at the pore edges. It is concluded, furthermore, that temperature mapping represents a useful new tool with which to optimise the process of nail poration. The method is potentially generic and may be applicable to other biological materials.

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          Most cited references33

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          Neurosurgery: functional regeneration after laser axotomy.

          Understanding how nerves regenerate is an important step towards developing treatments for human neurological disease, but investigation has so far been limited to complex organisms (mouse and zebrafish) in the absence of precision techniques for severing axons (axotomy). Here we use femtosecond laser surgery for axotomy in the roundworm Caenorhabditis elegans and show that these axons functionally regenerate after the operation. Application of this precise surgical technique should enable nerve regeneration to be studied in vivo in its most evolutionarily simple form.
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            Toenail onychomycosis treated with a fractional carbon-dioxide laser and topical antifungal cream.

            Traditional pharmacotherapy for onychomycosis has low to moderate efficacy and may be associated with adverse reactions and medication interactions limiting its use in many patients. We evaluated the clinical efficacy and safety of a fractional carbon-dioxide laser with topical antifungal therapy in the treatment of onychomycosis. In all, 24 patients were treated with fractional carbon-dioxide laser therapy and a topical antifungal cream. The laser treatment consisted of 3 sessions at 4-week intervals. Efficacy was assessed based on the response rate from standardized photographs, a microscopic examination of subungual debris, and subjective evaluations. Among the patients, 92% showed a clinical response and 50% showed a complete response with a negative microscopic result. The factors that influenced a successful outcome were the type of onychomycosis and the thickness of the nail plate before treatment. The treatment regimen was well tolerated and there was no recurrence 3 months after the last treatment episode. The study followed up only 24 patients and there were no relevant treatment controls. Fractional carbon-dioxide laser therapy, combined with a topical antifungal agent, was effective in the treatment of onychomycosis. It should be considered an alternative therapeutic option in patients for whom systemic antifungal agents are contraindicated. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
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              Next generation intra- and transdermal therapeutic systems: using non- and minimally-invasive technologies to increase drug delivery into and across the skin.

              The number of drug molecules approved by the regulatory authorities for transdermal administration is relatively modest - less than two dozen. Many other therapies might benefit from the advantages offered by the transdermal route. That they have not already done so is due to the exceptional efficacy of the stratum corneum as a diffusional barrier and its remarkable ability to restrict molecular transport. As a result only extremely potent therapeutics possessing the necessary physicochemical properties can be delivered by passive diffusion across intact skin at pharmacologically relevent rates. This has led to the development of several delivery technologies that might be used to expand the range of medicinal agents that can be administered transdermally with the requisite delivery kinetics. There are essentially two approaches: (i) provide an improved driving force to increase the rate of transport (i.e., act on the molecule) or (ii) modify the properties of the microenvironment through which diffusion must occur (i.e., act on the stratum corneum). The challenge for the latter approach is to compromise the barrier in a reversible and relatively painless manner that minimises irritation, is practical for chronic conditions and has minimal risk of infection. Here, we review some of the physical methods that have been used to either transiently perturb the skin barrier or to provide additional driving forces to facilitate molecular transport with a particular focus on technologies that have either led to marketed products or have at least reached the clinical development stage. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                r.h.guy@bath.ac.uk
                Journal
                Drug Deliv Transl Res
                Drug Deliv Transl Res
                Drug Delivery and Translational Research
                Springer US (New York )
                2190-393X
                2190-3948
                23 April 2019
                23 April 2019
                2019
                : 9
                : 5
                : 956-967
                Affiliations
                [1 ]ISNI 0000 0001 2162 1699, GRID grid.7340.0, Department of Physics, , University of Bath, ; Claverton Down, Bath, BA2 7AY UK
                [2 ]ISNI 0000 0001 2162 1699, GRID grid.7340.0, Department of Pharmacy & Pharmacology, , University of Bath, ; Claverton Down, Bath, BA2 7AY UK
                [3 ]ISNI 0000 0001 2162 1699, GRID grid.7340.0, Centre for Nanoscience & Nanotechnology, , University of Bath, ; Claverton Down, Bath, BA2 7AY UK
                [4 ]ISNI 0000 0001 2162 1699, GRID grid.7340.0, Centre for Therapeutic Innovation and Centre for Biosensors, Bioelectronics & Biodevices, , University of Bath, ; Claverton Down, Bath, BA2 7AY UK
                Author information
                http://orcid.org/0000-0003-3227-9862
                Article
                638
                10.1007/s13346-019-00638-x
                6731198
                31016477
                604fdba6-b346-44b8-8f00-5982e91e72b3
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: University of Bath
                Categories
                Original Article
                Custom metadata
                © Controlled Release Society 2019

                Pharmacology & Pharmaceutical medicine
                human nail,femtosecond pulsed laser ablation,nail poration,fluorescence microscopy,thermal mapping,drug delivery

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