Abstract
Atopic dermatitis (AD) is caused by multiple factors that trigger chronic skin inflammation, including a defective skin barrier, immune cell activation, and microbial exposure. Although melatonin has an excellent biosafety profile and a potential to treat AD, there is limited clinical evidence from controlled trials that support the use of melatonin as an AD treatment. The delivery of melatonin via the transdermal delivery system is also a challenge in designing melatonin-based AD treatments. In this study, we generated melatonin-loaded extracellular vesicle-mimetic nanoparticles (MelaNVs) to improve the transdermal delivery of melatonin and to evaluate their therapeutic potential in AD. The MelaNVs were spherical nanoparticles with an average size of 100 nm, which is the optimal size for the transdermal delivery of drugs. MelaNVs showed anti-inflammatory effects by suppressing the release of TNF-α and β-hexosaminidase in LPS-treated RAW264.7 cells and compound 48/80-treated RBL-2H3 cells, respectively. MelaNVs showed a superior suppressive effect compared to an equivalent concentration of free melatonin. Treating a 2,4-dinitrofluorobenzene (DNCB)-induced AD-like mouse model with MelaNVs improved AD by suppressing local inflammation, mast cell infiltration, and fibrosis. In addition, MelaNVs effectively suppressed serum IgE levels and regulated serum IFN-γ and IL-4 levels. Taken together, these results suggest that MelaNVs are novel and efficient transdermal delivery systems of melatonin and that MelaNVs can be used as a treatment to improve AD.
Highlights
The precise pathogenesis of Atopic dermatitis (AD) has yet to be fully elucidated, a defective skin barrier, immune cell activation, and environmental factors are known to be involved in the progression of AD [37]
We demonstrated that melatonin suppresses high glucose- or p-Cresol-induced fibrosis in human renal proximal tubule epithelial cells [39,40]
We hypothesized that melatonin-loaded Extracellular vesicles (EVs) mimetics would have excellent inhibitory effects on AD
Summary
Atopic dermatitis (AD) is a skin disease characterized by a chronic inflammation of the skin. AD usually occurs in early childhood, and symptoms can persist even in adulthood. The disease burden of AD is increasing worldwide, with approximately 20%. AD causes pruritus, dryness, and other skin lesions, including serious exudate, excoriation, patches, and lichenification [3]. The symptoms may disappear with age; most children are affected by other atopic diseases, such as allergic rhinitis and asthma [4–6]. The pathogenesis of AD involves the dysfunction of the skin barrier and inflammation, which are influenced by various environmental, immunological, and genetic factors. A recent study found that genetic defects of filaggrin, Biomolecules 2021, 11, 1450.
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