Subcytotoxic transepidermal delivery using low intensity cold atmospheric plasma

Area of Science:

• Biomedical Engineering
• Dermatology
• Plasma Physics

Background:

• Cold atmospheric plasma (CAP) utilizes oxidative properties for medical applications.
• Recent research indicates CAP can enhance transdermal delivery of large molecules.
• Low-intensity CAP (LICAP) offers controlled, sub-toxic plasma levels for biological benefits.

Purpose of the Study:

• To determine the sub-cytotoxic exposure time range for LICAP.
• To investigate LICAP's effect on transepidermal drug delivery (TED) and its mechanisms.
• To evaluate LICAP's safety and efficacy in vitro and in vivo models.

Main Methods:

• In vitro: Assessed reactive species, DNA damage, and cytotoxicity in human keratinocytes (HaCaT) exposed to LICAP.
• Mechanistic studies: Quantified tight/adherens junction gene expression and analyzed HaCaT morphology.
• In vivo: Examined E-cadherin expression and hEGF delivery in LICAP-treated mouse skin.

Main Results:

• The upper safety limit for LICAP exposure was determined at 34.3 seconds (IC70).
• LICAP downregulated tight and adherens junction genes in HaCaT cells, creating intercellular clefts.
• LICAP treatment reduced E-cadherin in mouse skin, facilitating hEGF dermal infiltration and FITC-dextran uptake.

Conclusions:

• LICAP treatment effectively enhances transepidermal permeation of hEGF via paracellular and transcellular routes.
• LICAP presents a novel, low-toxicity approach for facilitating transdermal drug delivery in vitro.
• Further clinical studies are warranted to evaluate LICAP's therapeutic potential.