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


METHODS
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.


RESULTS
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.


CONCLUSIONS
We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.
School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan.
Yin-Ku
YK
Lin
School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Sien-Hung
SH
Yang
Molecular Genetics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Chin-Chuan
CC
Chen
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Hsiao-Ching
HC
Kao
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Jia-You
JY
Fang
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000077271:Imiquimod; D051379:Mice; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D014212:Tretinoin / Q000008:administration & dosage / Q000493:pharmacokinetics
D000634:Aminoquinolines; D016207:Cytokines; D014212:Tretinoin; D000622:Aminolevulinic Acid; D000077271:Imiquimod; D016559:Tacrolimus