title: The risk of hydroquinone and sunscreen over-absorption via photodamaged skin is not greater in senescent skin as compared to young skin: nude mouse as an animal model.
abstract: Intrinsic aging and photoaging modify skin structure and components, which subsequently change percutaneous absorption of topically applied permeants. The purpose of this study was to systematically evaluate drug/sunscreen permeation via young and senescent skin irradiated by ultraviolet (UV) light. Both young and senescent nude mice were subjected to UVA (10 J/cm(2)) and/or UVB radiation (175 mJ/cm(2)). Physiological parameters, immunohistology, and immunoblotting were employed to examine the aged skin. Hydroquinone and sunscreen permeation was determined by in vitro Franz cell. In vivo skin absorption was documented using a hydrophilic dye, rhodamine 123 (log P=-0.4), as a permeant. UVA exposure induced cyclooxygenase (COX)-2 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) upregulation. Epidermal tight junction (TJ) were degraded by UVA. UVB increased transepidermal water loss (TEWL) from 13 to 24 g/m(2)/h. Hyperplasia and inflammation, but not loss of TJ, were also observed in UVB-treated skin. UVA+UVB- and UVA-irradiated skin demonstrated similar changes in histology and biomarkers. UVA+UVB or UVA exposure increased hydroquinone flux five-fold. A negligible alteration of hydroquinone permeation was shown with UVB exposure. Hydroquinone exhibited a lower penetration through senescent skin than young skin. Both UVA and UVB produced enhancement of oxybenzone flux and skin uptake. However, the amount of increase was less than that of hydroquinone delivery. Photoaging did not augment skin absorption of sunscreens with higher lipophilicity, including avobenzone and ZnO. Exposure to UVA generally increased follicular entrance of these permeants, which showed two- to three-fold greater follicular uptake compared to the untreated group. Photoaging had less impact on drug/sunscreen absorption with more lipophilic permeants. Percutaneous absorption did not increase in skin subjected to both intrinsic and extrinsic aging.
authors.affiliation: School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
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; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Shih
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; D015820:Cadherins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D018859:Hair Follicle / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006873:Hydroquinones / Q000493:pharmacokinetics*; D007633:Keratins / Q000378:metabolism; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D012869:Skin Absorption / Q000187:drug effects / Q000528:radiation effects*; D015595:Skin Aging / Q000528:radiation effects*; D013473:Sunscreening Agents / Q000493:pharmacokinetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D015820:Cadherins; D006360:Heat-Shock Proteins; D006873:Hydroquinones; D013473:Sunscreening Agents; D007633:Keratins; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C031927:hydroquinone
keywords: Hydroquinone; Intrinsic aging; Percutaneous absorption; Photoaging; Sunscreen; Tight junction