Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

Background and ObjectiveAblative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. Materials and MethodsMTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n=120). A 2,940nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11mJ/channel, MAZ-E), superficial-dermis (26mJ/channel, MAZ-DS), and mid-dermis (256mJ/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 (254nm) and semi-quantify MTX distribution in skin. ResultsAFXL increased topical MTX-delivery (P<0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07mg/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: 1.85mg/cm(3) at 500m skin-level vs. MAZ-DM: 3.75mg/cm(3) at 800m, 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 (6-47m, P0.438). ConclusionAFXL 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. (c) 2016 Wiley Periodicals, Inc.