Abstract

Contact dermatitis produces an inflammatory reaction primarily via stimulation of keratinocytes and cells of the immune system, which promote the release of cytokines, reactive oxygen species (ROS), and other chemical mediators. Eugenol (EUG, phenylpropanoid of essential oils) has attracted attention due to its anti-inflammatory properties, as well as antioxidant effect. On the other hand, it is volatile and insoluble and is a skin irritant. In this case, nanostructured systems have been successfully employed as a drug carrier for skin diseases since they improve both biological and pharmaceutical properties of active compounds. The cytotoxic, antioxidant, and anti-inflammatory effects of EUG were assessed in human neutrophils and keratinocytes. Additionally, polymeric nanocarries (NCEUG) were prepared to improve the chemical and irritant characteristics of EUG. EUG presented apparent safety and antioxidant and anti-inflammatory effects on human neutrophils, but presented cytotoxic effects on keratinocytes. However, the nanocapsules were able to reduce its cytotoxicity. An in vivo experiment of irritant contact dermatitis (ICD) in mice induced by TPA showed that NCEUG reduced significantly the ear edema in mice when compared to the EUG solution, as well as the leukocyte infiltration and IL-6 level, possibly due to better skin permeation and irritancy blockage. These findings suggest that EUG is a promising bioactive molecule, and its nanoencapsulation seems to be an interesting approach for the treatment of ICD.

Highlights

  • Contact dermatitis accounts for 70–90% of all occupational skin diseases and describes the allergic skin reaction resulting from exposure to irritants (irritant contact dermatitis (ICD)) or to allergens (allergic contact dermatitis (ACD)) [1].Several alterations are observed in epidermal cells during ICD

  • In order to verify the possible cytotoxicity of EUG, we investigated its effects on cellular metabolism with the MTT test and cell membrane integrity in human neutrophils

  • Some assays may be used to investigate the possible effect of drugs on the pattern of cell death including the detection of cell morphological changes by light microscopy, electron microscopy, or flow cytometry [42]

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Summary

Introduction

Several alterations are observed in epidermal cells during ICD. In some cases, such changes are limited to the superficial layers of the epidermis. In the course of the inflammatory process, the production of IL-8 by keratinocytes with consequent recruitment of polymorphonuclear neutrophils (PMNs) accumulates in the damaged epidermis, leading to the formation of intraepidermal pustules [2]. ROS are set free by inflammatory mediators, generated directly by irritants [3,4,5], and released during free radical chain reactions. The main source of ROS is inflammatory cellular infiltrate. Stimulated cells produce superoxide; the respiratory burst of infiltrating PMNs in inflamed skin will produce high local levels of superoxide anion and hydrogen peroxide.

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