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

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 UVand 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 AGE (2015) 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.

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…Mortality rates due to skin-related diseases and cancer are on the rising side, even in this era of modern medicine (Juckett 2010). Almost all of the available sunscreens elicit protection against UV-B (Burke and Wei 2009), even though UV-A is known to reach earth predominantly than UV-B (Hung et al 2015) and also cause detrimental effects. So there is a far cry need to find strategies to inhibit the action of UV-A on biological systems.…”

“…However, the role of UV-A, in eliciting photoaging, is less studied. As UV-A is 10 to 100 times abundant in natural sunlight and because of its capacity to penetrate the skin more deeply than UV-B (Hung et al 2015), it is necessary to focus more on UV-A-mediated photoaging process.…”

“…UV-A exposure to the skin of nude mice causes pale coloring of the skin that lead to decreased blood supply and eventually to apoptosis and necrosis (Hung et al 2015). A recent study used hen as a model to check the level of vitamin D in eggs upon exposure to UV radiation (Kuhn et al 2015).…”

The impact of aging on epithelial barriers

“…UV exposure of skin (photoaging) is associated with decreased E-cadherin and b-catenin expression and was exacerbated in ovariectomized mice that simulate menopause. 49 These changes in adhesion molecule expression were associated with increased skin permeability to tretinoin, a lipophilic compound. Conversely, other studies have shown that intrinsic and photoaging did not increase skin absorption of rhodamine123 or hydroquinone, despite alterations in TJ components.…”

The atopic dermatitis-like lesion and the associated MRSA infection and barrier dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from Antrodia camphorata

“…The real-time PCR was performed using iQ SYBR Green Supermix according to the manufacturer's instructions. The primers used to analyze mRNA were the same as in the previous report [15].…”