title: The impact of urban particulate pollution on skin barrier function and the subsequent drug absorption.
abstract: BACKGROUND
  Ambient particulate matters (PMs) are known as inducers that adversely affect a variety of human organs.
  
  
  OBJECTIVE
  In this study, we aimed to evaluate the influence of PMs on the permeation of drugs and sunscreens via the skin. The role of skin-barrier properties such as the stratum corneum (SC) and tight junctions (TJs) during the delivery process was explored.
  
  
  METHODS
  This work was conducted using both in vitro and in vivo experiments in pigs to check the responses of the skin to PMs. PMs primarily containing heavy metals (1648a) and polycyclic aromatic hydrocarbons (PAHs, 1649b) were employed to treat the skin.
  
  
  RESULTS
  According to the transepidermal water loss (TEWL), 1649b but not 1648a significantly disrupted the SC integrity by 2-fold compared to the PBS control. The immunohistochemistry (IHC) of cytokeratin, filaggrin, and E-cadherin exhibited that 1649b mildly damaged TJs. The cytotoxicity of keratinocytes and skin fibroblasts caused by 1649b was stronger than that caused by 1648a. The 1649b elicited apoptosis via caspase-3 activation. The proteomic profiles showed that PMs upregulated Annexin A2 by >5-fold, which can be a biomarker of PM-induced barrier disruption. We found that the skin uptake of ascorbic acid, an extremely hydrophilic drug, was increased from 74 to 112 μg/g by 1649b treatment. The extremely lipophilic drug tretinoin also showed a 2.6-fold increase of skin accumulation. Oxybenzone and dextran absorption was not affected by PMs. The in vivo dye distribution visualized by fluorescence microscopy had indicated that 1649b intervention promoted permeant partitioning into SC.
  
  
  CONCLUSIONS
  Caution should be taken in exposing the skin to airborne dust due to its ability to reduce barrier function and increase the risk of drug overabsorption, although this effect was not very marked.
authors: School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
authors: Tai-Long
authors: TL
authors: Pan
authors: School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
authors: Pei-Wen
authors: PW
authors: Wang
authors: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors: Ibrahim A
authors: IA
authors: Aljuffali
authors: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors: Chi-Ting
authors: CT
authors: Huang
authors: Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan. Electronic address: cwlee@gw.cgust.edu.tw.
authors: Chiang-Wen
authors: CW
authors: Lee
authors: Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
authors: Jia-You
authors: JY
authors: Fang
mesh_terms: D000279:Administration, Cutaneous; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000493:pharmacokinetics; D001577:Benzophenones / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003911:Dextrans / Q000493:pharmacokinetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D000091344:Filaggrin Proteins; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019216:Metals, Heavy / Q000633:toxicity; D023421:Models, Animal; D052638:Particulate Matter / Q000633:toxicity*; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects*; D034421:Sus scrofa; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000493:pharmacokinetics; D014870:Water Loss, Insensible / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D001577:Benzophenones; D003911:Dextrans; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D019216:Metals, Heavy; D052638:Particulate Matter; D004364:Pharmaceutical Preparations; D011084:Polycyclic Aromatic Hydrocarbons; D014212:Tretinoin; C005290:oxybenzone; D001205:Ascorbic Acid
keywords: Barrier function; Drug absorption; Particulate matter; Skin; Stratum corneum; Tight junction