Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation

TY - JOUR

T1 - Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation

AU - Taudorf, Elisabeth Hjardem

AU - Lerche, Catharina

AU - Vissing, Anne-Cathrine

AU - Philipsen, Peter Alshede

AU - Hannibal, Jens

AU - D'Alvise, Ulla Janina Christin

AU - Hansen, Steen Honoré

AU - Janfelt, Christian

AU - Paasch, Uwe

AU - Anderson, R Rox

AU - Hædersdal, Merete

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Objectives: 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).Methods: 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.Results: 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/cm3, 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.Conclusions: 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.

AB - Objectives: 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).Methods: 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.Results: 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/cm3, 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.Conclusions: 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.

U2 - 10.1517/17425247.2015.1031216

DO - 10.1517/17425247.2015.1031216

M3 - Journal article

C2 - 25893560

SN - 1742-5247

VL - 12

SP - 1059

EP - 1069

JO - Expert Opinion on Drug Delivery

JF - Expert Opinion on Drug Delivery

IS - 7

ER -