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

Abstract

ObjectivePsoriasis 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.MethodsWe 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.ResultsThe 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.ConclusionWe established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.

Antiproliferation of keratinocytes and alleviation of psoriasis by the ethanol extract of Artemisia capillaris

“…Topical application of IMQ on the mouse skin can generate human psoriasis‐like lesions with similar phenotypic, histological, and inflammatory characteristics (Lin, Yang, Chen, Kao, & Fang, ; van der Fits et al, ). That model exhibits following properties, such as increase of erythema, increase in transepidermal water loss (TEWL), decrease in skin surface pH, desquamation, epidermal hyperproliferation, the overexpression of IL‐17, IL‐23, and tumor necrosis factor (TNF)‐α, and infiltration of CD‐3 cells (Lin et al, ; van der Fits et al, ).…”

Comparison of normal versus imiquimod-induced psoriatic skin in mice for penetration of drugs and nanoparticles

“…However, there are few studies to investigate and compare the penetration behaviors of drugs and nanoparticles (NPs) formulation in psoriatic skin, the understanding of which may ultimately affect the design and development of anti-psoriatic topical formulations. In 2015, imiquimod (IMQ)-induced psoriatic skin (IMQ-psoriatic skin) was utilized to estimate the in vitro penetration behavior of drugs by Lin et al 12 for the first time, whose research demonstrated much higher penetration of drug through IMQ-psoriatic skin, than through normal skin. The study also showed that the lipophilicity of a drug dictated the permeation behaviors of the drug in IMQ-psoriatic lesions.…”

Imiquimod-induced psoriasis-like skin inflammation in mouse model

“…Imiquimod is also used to induce psoriasis to measure the skin penetration of some anti-psoriatic drugs (Lin et al, 2015).…”