Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate
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Fractional laser-assisted drug delivery : Laser channel depth influences biodistribution and skin deposition of methotrexate. / Taudorf, Elisabeth Hjardem; Lerche, C.M.; Erlendsson, A M; Philipsen, P A; Hansen, Steen Honoré; Janfelt, C; Paasch, U; Anderson, R R; Haedersdal, M.
In: Lasers in Surgery and Medicine, Vol. 48, No. 5, 07.2016, p. 519-529.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Fractional laser-assisted drug delivery
T2 - Laser channel depth influences biodistribution and skin deposition of methotrexate
AU - Taudorf, Elisabeth Hjardem
AU - Lerche, C.M.
AU - Erlendsson, A M
AU - Philipsen, P A
AU - Hansen, Steen Honoré
AU - Janfelt, C
AU - Paasch, U
AU - Anderson, R R
AU - Haedersdal, M
N1 - © 2016 Wiley Periodicals, Inc.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
U2 - 10.1002/lsm.22484
DO - 10.1002/lsm.22484
M3 - Journal article
C2 - 26846733
VL - 48
SP - 519
EP - 529
JO - Lasers in Surgery and Medicine
JF - Lasers in Surgery and Medicine
SN - 0196-8092
IS - 5
ER -
ID: 169384242