TY - JOUR
T1 - Using imiquimod-induced psoriasis-like skin as a model to measure the skin penetration of anti-psoriatic drugs
AU - Lin, Yin Ku
AU - Yang, Sien Hung
AU - Chen, Chin Chuan
AU - Kao, Hsiao Ching
AU - Fang, Jia You
N1 - Publisher Copyright:
© 2015 Lin et al.
PY - 2015/9/10
Y1 - 2015/9/10
N2 - 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 phenotypi-cal 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. Conclusion: We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.
AB - 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 phenotypi-cal 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. Conclusion: We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.
UR - https://www.scopus.com/pages/publications/84944811018
U2 - 10.1371/journal.pone.0137890
DO - 10.1371/journal.pone.0137890
M3 - 文章
C2 - 26355594
AN - SCOPUS:84944811018
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0137890
ER -