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• W2024862045 abstract "Methotrexate (MTX) is a chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects. This study investigated kinetics and biodistribution of MTX delivered topically by ablative fractional laser (AFXL).In vitro passive diffusion of 10 mg/ml MTX (1 w/v%) was measured from 0.25 to 24 h through AFXL-processed and intact porcine skin in Franz Cells (n = 46). A 2,940 nm fractional Erbium Yttrium Aluminium Garnet laser generated mid-dermal microchannels at 2.4% density, and 256 mJ/microchannel. HPLC quantified MTX-concentrations in extracts from mid-dermal skin sections, donor and receiver compartments. Fluorescence microscopy of UVC-activated MTX-fluorescence and desorption electro-spray ionization mass spectrometry imaging (DESI-MSI) evaluated MTX biodistribution.AFXL-processed skin facilitated rapid MTX delivery through cone-shaped microchannels of 690 µm ablation depth, lined by the 47 µm thermal coagulation zone (CZ). Quantitatively, MTX was detectable by HPLC in mid-dermis after 15 min, significantly exceeded deposition in intact skin after 1.5 h, and saturated skin after 7 h at a 10-fold increased MTX-deposition versus intact skin (3.08 vs 0.30 mg/cm(3), p = 0.002). Transdermal permeation was < 1.5% of applied MTX before skin saturation, and increased up to 8.0% after 24 h. Qualitatively, MTX distributed into CZ within 15 min (p = 0.015) and further into surrounding dermal tissue after 1.5 h (p = 0.004). After skin saturation at 7 h, MTX fluorescence intensities in CZ and tissue were similar and DESI-MSI confirmed MTX biodistribution throughout the mid-dermal skin section.MTX absorbs rapidly into mid-dermis of AFXL-processed skin with minimal transdermal permeation until skin saturation, suggesting a possible alternative to systemic MTX for some skin disorders." @default.
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• W2024862045 date "2015-04-20" @default.
• W2024862045 modified "2023-09-26" @default.
• W2024862045 title "Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation" @default.
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• W2024862045 doi "https://doi.org/10.1517/17425247.2015.1031216" @default.
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