Topical delivery of methotrexate via skin pretreated with physical enhancement techniques: Low-fluence erbium:YAG laser and electroporation

Woan Ruoh Lee, Shin Chuan Shen, Chia Lang Fang, Rou Zi Zhuo, Jia You Fang

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background and Objective: The high hydrophilicity and molecular weight of methotrexate (MTX) make it difficult to deliver via the skin route for treating psoriasis or rheumatoid arthritis. The objective of this study was to enhance and optimize the skin permeation of MTX using two physical techniques: an erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation. Methods: In vitro skin permeation was performed using horizontal side-by-side diffusion cells. The animal model utilized nude mice. The skin where epidermal hyperproliferation was reproduced by repeated barrier abrogation was also used as a permeation barrier for MTX delivery. Results: Application of the laser and electroporation significantly enhanced the permeation of MTX. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the laser fluence. Using electroporation, treatment with 10 pulses resulted in a twofold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 minutes resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence (1.4 J/cm2) was applied. Hyperproliferative skin generally showed a greater variability of MTX flux and lower permeation. Conclusion: The results shown in the present study encourage further investigation of laser- and electroporation-assisted topical drug delivery.

Original languageEnglish
Pages (from-to)468-476
Number of pages9
JournalLasers in Surgery and Medicine
Volume40
Issue number7
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Electroporation
Solid-State Lasers
Methotrexate
Lasers
Skin
Erbium
Hydrophobic and Hydrophilic Interactions
Psoriasis
Nude Mice
Pharmaceutical Preparations
Rheumatoid Arthritis
Animal Models
Molecular Weight

Keywords

  • Electroporation
  • Er:YAG laser
  • Hyperproliferation
  • Methotrexate
  • Topical delivery

ASJC Scopus subject areas

  • Surgery

Cite this

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title = "Topical delivery of methotrexate via skin pretreated with physical enhancement techniques: Low-fluence erbium:YAG laser and electroporation",
abstract = "Background and Objective: The high hydrophilicity and molecular weight of methotrexate (MTX) make it difficult to deliver via the skin route for treating psoriasis or rheumatoid arthritis. The objective of this study was to enhance and optimize the skin permeation of MTX using two physical techniques: an erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation. Methods: In vitro skin permeation was performed using horizontal side-by-side diffusion cells. The animal model utilized nude mice. The skin where epidermal hyperproliferation was reproduced by repeated barrier abrogation was also used as a permeation barrier for MTX delivery. Results: Application of the laser and electroporation significantly enhanced the permeation of MTX. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the laser fluence. Using electroporation, treatment with 10 pulses resulted in a twofold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 minutes resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence (1.4 J/cm2) was applied. Hyperproliferative skin generally showed a greater variability of MTX flux and lower permeation. Conclusion: The results shown in the present study encourage further investigation of laser- and electroporation-assisted topical drug delivery.",
keywords = "Electroporation, Er:YAG laser, Hyperproliferation, Methotrexate, Topical delivery",
author = "Lee, {Woan Ruoh} and Shen, {Shin Chuan} and Fang, {Chia Lang} and Zhuo, {Rou Zi} and Fang, {Jia You}",
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T1 - Topical delivery of methotrexate via skin pretreated with physical enhancement techniques

T2 - Low-fluence erbium:YAG laser and electroporation

AU - Lee, Woan Ruoh

AU - Shen, Shin Chuan

AU - Fang, Chia Lang

AU - Zhuo, Rou Zi

AU - Fang, Jia You

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N2 - Background and Objective: The high hydrophilicity and molecular weight of methotrexate (MTX) make it difficult to deliver via the skin route for treating psoriasis or rheumatoid arthritis. The objective of this study was to enhance and optimize the skin permeation of MTX using two physical techniques: an erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation. Methods: In vitro skin permeation was performed using horizontal side-by-side diffusion cells. The animal model utilized nude mice. The skin where epidermal hyperproliferation was reproduced by repeated barrier abrogation was also used as a permeation barrier for MTX delivery. Results: Application of the laser and electroporation significantly enhanced the permeation of MTX. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the laser fluence. Using electroporation, treatment with 10 pulses resulted in a twofold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 minutes resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence (1.4 J/cm2) was applied. Hyperproliferative skin generally showed a greater variability of MTX flux and lower permeation. Conclusion: The results shown in the present study encourage further investigation of laser- and electroporation-assisted topical drug delivery.

AB - Background and Objective: The high hydrophilicity and molecular weight of methotrexate (MTX) make it difficult to deliver via the skin route for treating psoriasis or rheumatoid arthritis. The objective of this study was to enhance and optimize the skin permeation of MTX using two physical techniques: an erbium:yttrium-aluminum-garnet (Er:YAG) laser and electroporation. Methods: In vitro skin permeation was performed using horizontal side-by-side diffusion cells. The animal model utilized nude mice. The skin where epidermal hyperproliferation was reproduced by repeated barrier abrogation was also used as a permeation barrier for MTX delivery. Results: Application of the laser and electroporation significantly enhanced the permeation of MTX. The enhancing effect was more pronounced after applying the laser. Er:YAG laser pretreatment on the skin produced a 3- to 80-fold enhancement dependent upon the magnitude of the laser fluence. Using electroporation, treatment with 10 pulses resulted in a twofold increase in MTX flux. A combination of laser pretreatment and subsequent electroporation for 10 minutes resulted in a higher drug permeation than either technique alone. However, this synergistic effect was only observed when the lower laser fluence (1.4 J/cm2) was applied. Hyperproliferative skin generally showed a greater variability of MTX flux and lower permeation. Conclusion: The results shown in the present study encourage further investigation of laser- and electroporation-assisted topical drug delivery.

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