title: What is the discrepancy between drug permeation into/across intact and diseased skins? Atopic dermatitis as a model.
abstract: 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/m(2)/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.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Fang
authors.affiliation: School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
authors.forename: Sien-Hung
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Dermatology, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Kao
authors.affiliation: 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. Electronic address: fajy@mail.cgu.edu.tw.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D003911:Dextrans / Q000378:metabolism; D000091344:Filaggrin Proteins; D008727:Methotrexate / Q000378:metabolism; D008730:Methoxsalen / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D008954:Models, Biological; D010047:Ovalbumin; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D012869:Skin Absorption; D016559:Tacrolimus / Q000378:metabolism; D014870:Water Loss, Insensible
chemical_list: D016207:Cytokines; D003911:Dextrans; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D004364:Pharmaceutical Preparations; D010047:Ovalbumin; D008730:Methoxsalen; D016559:Tacrolimus; D008727:Methotrexate
keywords: Atopic dermatitis; Diseased skin; Percutaneous absorption; Stratum corneum; Tight junction