Treatment with low-temperature atmospheric pressure plasma enhances cutaneous delivery of epidermal growth factor by regulating E-cadherin-mediated cell junctions

Abstract

The barrier system of the skin not only defends against antigens and harmful substances, but also hinders the permeation of medicines and cosmetics into the dermis. Several strategies have been developed to enhance the absorption ability of skin, including the use of chemicals and skin ablation devices. However, the cost and inconvenience of these strategies highlights the need for a novel and safe method for increasing skin absorption. In this study, we examined the effect of low temperature atmospheric pressure plasma (LTAPP) on the efficiency of drug penetration through the skin, as well as its mechanism of action. HaCaT human keratinocytes and hairless mice were exposed to LTAPP treatment, and the cellular and tissue gene expression, and morphological changes were monitored. We found that the LTAPP exposure reduced the expression of E-cadherin in skin cells and led to the loss of cell-cell contacts. The exposure of mouse skin to LTAPP also reduced the expression of E-cadherin and prevented intercellular junction formation within the tissue, leading to enhanced absorption of hydrophilic agents, eosin and epidermal growth factor. The reduction in E-cadherin expression and reduced skin barrier function recovered completely within 3 h of LTAPP exposure. Taken together, these data show that LTAPP can induce a temporal decrease in the skin barrier function by regulating E-cadherin-mediated intercellular interactions, leading to the enhanced transdermal delivery of drugs and cosmetics.

Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma

“…In our previous report, we reported that the NTP treatment on skin increased the absorption rate of external EGF through the skin33. Considering this transdermal drug delivery promoting property of NTP, we suggest that the pre-treatment of skin with NTP before the application of HC might bring grater curative results.…”

Skin renewal activity of non-thermal plasma through the activation of β-catenin in keratinocytes

“…We previously reported that NTP treatment of keratinocytes caused the translocation of E-cadherin from cell border regions to the cytosol 27 . This suggested the possibility that keratinocytes could escape from the contact inhibition of cell growth.…”

“…However, despite many reports, the mechanism underlying NTP-mediated regeneration of skin tissue is not fully understood. We previously reported that NTP treatment modulated skin barrier function by inhibiting E-cadherin-mediated cellular interactions 27 . Given that E-cadherin is important for the formation of the skin barrier system and the regulation of keratinocyte proliferation, it has been suggested that NTP treatment might free keratinocytes from E-cadherin-mediated growth inhibition.…”

The topical application of low-temperature argon plasma enhances the anti-inflammatory effect of Jaun-ointment on DNCB-induced NC/Nga mice

“…LTAPP not only stimulates wound healing and skin surface decontamination [29, 30], but has also been suggested to be used for the cancer treatments [31, 32]. Furthermore, our previous study and the findings of Lademann et al, highlighted the safe and efficient transdermal drug delivery using LTAPP [33, 34]. Unlike other physical drug delivery systems, LTAPP can enhance drug absorption by temporary scattering cell-to-cell bonding in the epidermis, without harming tissues.…”

“…The Vapp of the plasma-treating mode is about 3 kV, and 2 slm (standard litters per minutes) of pure argon gas was used as a vehicle gas. Unlike the device in our previous reports [34], this new device produces the plasma glow only within plasma producing aisle, so that the plasma can’t contact to the skin directly. However, the device helped transdermal drug delivery activity effectively (Data not shown).…”