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Skin aging modulates percutaneous drug absorption: the impact of ultraviolet irradiation and ovariectomy

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Abstract

Ultraviolet (UV) exposure and menopause are known as the inducers of damage to the skin structure. The combination of these two factors accelerates the skin aging process. In this study, we aimed to evaluate the influence of UV and ovariectomy (OVX) on the permeation of drugs through the skin. The role of tight junctions (TJs) and adherens junctions (AJs) in the cutaneous absorption of extremely lipophilic permeants and macromolecules was explored. The OVX nude mouse underwent bilateral ovary removal. Both UVA and UVB were employed to irradiate the skin. The physiological and biochemical changes of the skin structure were examined with focus on transepidermal water loss (TEWL), skin color, immunohistochemistry, and mRNA levels of proteins. UVB and OVX increased TEWL, resulting in stratum corneum (SC) integrity disruption and dehydration. A hyperproliferative epidermis was produced by UVB. UVA caused a pale skin color tone due to keratinocyte apoptosis in the epidermis. E-cadherin and β-catenin showed a significant loss by both UVA and UVB. OVX downregulated the expression of filaggrin and involucrin. A further reduction was observed when UV and OVX were combined. The in vitro cutaneous absorption demonstrated that UV increased the skin permeation of tretinoin by about twofold. However, skin accumulation and flux of estradiol were not modified by photoaging. OVX basically revealed a negligible effect on altering the permeation of small permeants. OVX increased tretinoin uptake by the appendages from 1.36 to 3.52 μg/cm2. A synergistic effect on tretinoin follicular uptake enhancement was observed for combined UV and OVX. However, the intervention of OVX to photoaged skin resulted in less macromolecule (dextran, molecular weight = 4 kDa) accumulation in the skin reservoir because of retarded partitioning into dry skin. The in vivo percutaneous absorption of lipophilic dye examined by confocal microscopy had indicated that the SC was still important to controlling topical delivery, although the role of epidermal junctions could not be simply ignored.

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Acknowledgments

The authors are grateful to the financial support from Chang Gung Memorial Hospital (grant number: CMRPF1C0171).

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Authors and Affiliations

  1. School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei, Taiwan

    Chi-Feng Hung

  2. Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Wei-Yu Chen

  3. Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Wei-Yu Chen

  4. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Ibrahim A. Aljuffali

  5. Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan

    Yin-Ku Lin

  6. School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan

    Yin-Ku Lin

  7. Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, Taiwan

    Hui-Chi Shih & Jia-You Fang

  8. Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan

    Hui-Chi Shih

  9. Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan

    Jia-You Fang

  10. Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan

    Jia-You Fang

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  1. Chi-Feng Hung
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  4. Yin-Ku Lin
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Correspondence to Jia-You Fang.

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Hung, CF., Chen, WY., Aljuffali, I.A. et al. Skin aging modulates percutaneous drug absorption: the impact of ultraviolet irradiation and ovariectomy. AGE 37, 21 (2015). https://doi.org/10.1007/s11357-015-9757-1

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  • DOI: https://doi.org/10.1007/s11357-015-9757-1

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