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

Elisabeth Hjardem Taudorf; C.M. Lerche; A M Erlendsson; P A Philipsen; Steen Honoré Hansen; C Janfelt; U Paasch; R R Anderson; M Haedersdal

doi:10.1002/lsm.22484

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

Elisabeth Hjardem Taudorf, C.M. Lerche, A M Erlendsson, P A Philipsen, Steen Honoré Hansen, C Janfelt, U Paasch, R R Anderson, M Haedersdal

Institut for Klinisk Medicin

34 Citationer (Scopus)

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/cm², 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/cm³ at 500 μm skin-level vs. MAZ-DM: 3.75 mg/cm³ 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.

Originalsprog	Engelsk
Tidsskrift	Lasers in Surgery and Medicine
Vol/bind	48
Udgave nummer	5
Sider (fra-til)	519-529
Antal sider	11
ISSN	0196-8092
DOI	https://doi.org/10.1002/lsm.22484
Status	Udgivet - 1 jul. 2016

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10.1002/lsm.22484

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

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/cm2, 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/cm3 at 500 μm skin-level vs. MAZ-DM: 3.75 mg/cm3 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.",

author = "Taudorf, {Elisabeth Hjardem} and C.M. Lerche and Erlendsson, {A M} and Philipsen, {P A} and Hansen, {Steen Honor{\'e}} and C Janfelt and U Paasch and Anderson, {R R} and M Haedersdal",

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doi = "10.1002/lsm.22484",

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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

PY - 2016/7/1

Y1 - 2016/7/1

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/cm2, 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/cm3 at 500 μm skin-level vs. MAZ-DM: 3.75 mg/cm3 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.

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/cm2, 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/cm3 at 500 μm skin-level vs. MAZ-DM: 3.75 mg/cm3 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.

U2 - 10.1002/lsm.22484

DO - 10.1002/lsm.22484

M3 - Journal article

C2 - 26846733

SN - 0196-8092

VL - 48

SP - 519

EP - 529

JO - Lasers in Surgery and Medicine

JF - Lasers in Surgery and Medicine

IS - 5

ER -

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

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