Histological and immunohistochemical examination of mouse skin treated with and without imiquimod cream: (A) hemoxylin and eosin (H&E) staining; (B) the epidermal thickness measured by H&E staining; (C) CD3⁺ T cell staining; and (D) β-catenin.

<p>The control group corresponds to the mice treated with the vehicle.</p

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

<div><p>Objective</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.</p></div

The mRNA levels of cytokines and differentiation markers in mouse skin treated with and without imiquimod cream: (A) TNF-α; (B) IL-17A; (C) IL-23; (D) filaggrin; and (E) involucrin.

<p>The control group corresponds to the mice treated with the vehicle. The data are presented as the mean of six experiments±S.D. *, <i>p</i> < 0.05 between control and imiquimod groups.</p

Physicochemical properties of the drug molecules tested in this study.

<p>The physicochemical properties of all drugs were obtained from DrugBank website (<a href="http://www.drugbank.ca/" target="_blank">www.drugbank.ca/</a><i>)</i>.</p><p>Physicochemical properties of the drug molecules tested in this study.</p

Confocal micrographs of mouse skin treated with and without imiquimod cream: (A) the skin without topical application of permeants; (B) the skin topically applied with ALA; and (C) the skin topically applied with rhodamine B.

<p>The control group corresponds to the mice treated with the vehicle. Both the fragments from skin surface to the depth of 75 μm and a summary of 15 fragments at various skin depths are displayed in this figure. Scale bar = 150 μm.</p

The comparison of skin permeation profiles of 5-aminolevulinic acid, tacrolimus, calcipotriol, and retinoic acid via control and psoriasis-like skins.

<p>^a The control group corresponds to the mice treated with the vehicle.</p><p>^b Ratio_{psoriasis/control}, ratio of the permeation parameter of psoriatic skin/ permeation parameter of control skin.</p><p>^c ―, not determined.</p><p>Each value represents the mean and S.D. (<i>n</i> = 4).</p><p>The comparison of skin permeation profiles of 5-aminolevulinic acid, tacrolimus, calcipotriol, and retinoic acid via control and psoriasis-like skins.</p

Cytokine levels in normal and psoriatic skins.

<p>^a The control group corresponds to the mice treated with the vehicle.</p><p>Each value represents the mean and S.D. (<i>n</i> = 6).</p><p>Cytokine levels in normal and psoriatic skins.</p

Gross observation and physiological parameters of mouse skin treated with and without imiquimod cream: (A) the gross imaging by digital camera; (B) the gross imaging by handheld digital microscope; (C) transepidermal water loss (TEWL); (D) erythema; and (E) skin surface pH value.

<p>The control group corresponds to the mice treated with the vehicle. The data of physiological assessment are presented as the mean of six experiments±S.D. *, <i>p</i> < 0.05 between control and imiquimod groups.</p

Cumulative percentage-time profiles of drug permeation across intact and psoriasis-like skins: (A) ALA; (B) tacrolimus; (C) calcipotriol; and (D) retinoic acid.

<p>The data of are presented as the mean of four experiments±S.D.</p

BZYQT regulated Th2 cytokines in BALF of asthmatic murine model sensitized by OVA.

<p>The concentrations of IL-4 (A), IL-5 (B), and IL-13 (C) were determined by ELISA. Data were presented in mean ± standard deviation. * p < 0.05 compared with the OVA group.</p