Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.

<h4>Objective</h4>Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs.<h4>Methods</h4>We first s...

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Main Authors: Yin-Ku Lin, Sien-Hung Yang, Chin-Chuan Chen, Hsiao-Ching Kao, Jia-You Fang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0137890
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author Yin-Ku Lin
Sien-Hung Yang
Chin-Chuan Chen
Hsiao-Ching Kao
Jia-You Fang
author_facet Yin-Ku Lin
Sien-Hung Yang
Chin-Chuan Chen
Hsiao-Ching Kao
Jia-You Fang
author_sort Yin-Ku Lin
collection DOAJ
description <h4>Objective</h4>Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs.<h4>Methods</h4>We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption.<h4>Results</h4>The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin.<h4>Conclusion</h4>We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.
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spelling doaj.art-295ccc972e274d00968ab94c7243afbb2022-12-21T18:26:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013789010.1371/journal.pone.0137890Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.Yin-Ku LinSien-Hung YangChin-Chuan ChenHsiao-Ching KaoJia-You Fang<h4>Objective</h4>Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs.<h4>Methods</h4>We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption.<h4>Results</h4>The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin.<h4>Conclusion</h4>We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.https://doi.org/10.1371/journal.pone.0137890
spellingShingle Yin-Ku Lin
Sien-Hung Yang
Chin-Chuan Chen
Hsiao-Ching Kao
Jia-You Fang
Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
PLoS ONE
title Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
title_full Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
title_fullStr Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
title_full_unstemmed Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
title_short Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs.
title_sort using imiquimod induced psoriasis like skin as a model to measure the skin penetration of anti psoriatic drugs
url https://doi.org/10.1371/journal.pone.0137890
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