Skin aging modulates percutaneous drug absorption: the impact of ultraviolet irradiation and ovariectomy
| Autor: | Jia-You Fang, Hui Chi Shih, Yin Ku Lin, Ibrahim A. Aljuffali, Chi-Feng Hung, Wei Yu Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Aging
medicine.medical_specialty Ultraviolet Rays Photoaging Ovariectomy Mice Nude Enzyme-Linked Immunosorbent Assay Tretinoin Article Skin Aging Tight Junctions Mice Internal medicine Dry skin medicine Stratum corneum Animals Involucrin Skin Transepidermal water loss integumentary system Chemistry Reverse Transcriptase Polymerase Chain Reaction General Medicine Environmental exposure Adherens Junctions Environmental Exposure medicine.disease Dermatology Water Loss Insensible medicine.anatomical_structure Endocrinology Colorimetry Female Epidermis Geriatrics and Gerontology medicine.symptom Menopause |
| Popis: | 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/cm(2). 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. |
| Databáze: | OpenAIRE |
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