Fractional laser‐assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate. Issue 5 (5th February 2016)

• Record Type: Journal Article
• Authors: Taudorf, E.H.; Lerche, C.M.; Erlendsson, A.M.; Philipsen, P.A.; Hansen, S.H.; Janfelt, C.; Paasch, U.; Anderson, R.R.; Haedersdal, M.
• Is Part Of: Lasers in surgery and medicine. Volume 48:Issue 5(2016)
• Page Start: 519
• Page End: 529
• Publication Date: 2016-02-05
• Subjects: Er:Yag laser -- fluorescence microscopy -- Franz skin permeability Cells -- high performance liquid chromatography -- laser‐assisted drug delivery; Lasers in medicine -- Periodicals; Lasers in surgery -- Periodicals; 617
• DOI: 10.1002/lsm.22484
• Languages: English
• ISSNs: 0196-8092

Abstract

Abstract : Background and Objective: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser‐channel depth on topical MTX‐delivery. Materials and Methods: MTX (1% [w/v]) diffused for 21 hours through AFXL‐exposed porcine skin in in vitro Franz Cells ( n = 120). A 2, 940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ‐E), superficial‐dermis (26 mJ/channel, MAZ‐DS), and mid‐dermis (256 mJ/channel, MAZ‐DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full‐thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC‐activated MTX‐fluorescence (254 nm) and semi‐quantify MTX distribution in skin. Results: AFXL increased topical MTX‐delivery ( P < 0.001). Without laser exposure, MTX‐concentration in full‐thickness skin was 0.07 mg/cm 2, increasing sixfold (MAZ‐E), ninefold (MAZ‐DS), and 11‐fold (MAZ‐DM) after AFXL ( P < 0.001). Deeper MAZs increased MTX‐concentrations in all skin layers ( P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ‐E: 1.85 mg/cm 3 at 500 μm skin‐level vs. MAZ‐DM: 3.75 mg/cm 3 at 800 μm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth ( P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6–47 μm, P ≥ 0.438). Conclusion: AFXL greatly increases topical MTX‐delivery. Deeper MAZs deliver higher MTX‐concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519–529, 2016. © 2016 Wiley Periodicals, Inc.