What is the discrepancy between drug permeation into/across intact and diseased skins? Atopic dermatitis as a model

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• 作者：Yi-Ping Fang^a ; Sien-Hung Yang^b ; ^c ; Chih-Hung Lee^d ; ^e ; Ibrahim A. Aljuffali^f ; Hsiao-Ching Kao^g ; Jia-You Fang^g ; ^h ; ⁱ ; ^{fajy@mail.cgu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Atopic dermatitis ; Diseased skin ; Percutaneous absorption ; Stratum corneum ; Tight junction
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 January 2016
• 年：2016
• 卷：497
• 期：1-2
• 页码：277-286
• 全文大小：2640 K

文摘

The discrepancy in drug absorption between healthy and diseased skins is an issue that needs to be elucidated. The present study attempted to explore the percutaneous absorption of drugs via lesional skin by using atopic dermatitis (AD) as a model. Tape-stripping and ovalbumin (OVA) sensitization induced AD-like skin. The lesions were evaluated by physiological parameters, histology, cytokines, and differentiation proteins. The permeants of tacrolimus, 8-methoxypsoralen, methotrexate, and dextran were used to examine in vitro and in vivo cutaneous permeation. Transepidermal water loss (TEWL) increased from 5.2 to 27.4 g/m²/h by OVA treatment. AD-like lesions were characterized by hyperplasia, skin redness, desquamation, and infiltration of inflammatory cells. Repeated OVA challenge produced a T-helper 2 (Th2) hypersensitivity accompanied by downregulation of filaggrin, involucrin, and integrin β. Tacrolimus, the most lipophilic permeant, revealed an increase of cutaneous deposition by 2.7-fold in AD-like skin compared to intact skin. The transdermal flux of methotrexate and dextran, the hydrophilic permeants, across AD-like skin increased about 18 times compared to the control skin. Surprisingly, AD-like skin showed less skin deposition of 8-methoxypsoralen than intact skin. This may be because the deficient lipids in the atopic-affected stratum corneum (SC) diminished drug partitioning into the superficial skin layer. The fluorescence and confocal microscopic images demonstrated a broad and deep passage of small-molecular and macromolecular dyes into AD-like skin. The results obtained from this report were advantageous for showing how the lesional skin influenced percutaneous absorption.