Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation
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Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation. / Taudorf, Elisabeth Hjardem; Lerche, Catharina; Vissing, Anne-Cathrine; Philipsen, Peter Alshede; Hannibal, Jens; D'Alvise, Ulla Janina Christin; Hansen, Steen Honoré; Janfelt, Christian; Paasch, Uwe; Anderson, R Rox; Hædersdal, Merete.
In: Expert Opinion on Drug Delivery, Vol. 12, No. 7, 2015, p. 1059-1069.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2015
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
VL - 12
SP - 1059
EP - 1069
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
SN - 1742-5247
IS - 7
ER -
ID: 160863397