Avaliação do efeito de nanocápsulas contendo meloxicam na dermatite atópica induzida por 2,4-dinitroclorobenzeno em camundongos

Abstract

Atopic dermatitis (AD) is a complex chronic inflammatory skin disease that affects children and adults worldwide. Recommended therapy of AD has been the use of topical corticosteroids, topical calcineurin inhibitors, or both, for improving the symptoms and reducing the inflammation. Although available topical agents are generally well tolerated, their applications may cause side effects. Thus, there is a need for new effective topical treatment options without such safety concerns. A new alternative treatment of AD is the use of non-steroidal anti-inflammatories. Indeed, meloxicam is a highly potent non-steroidal anti-inflammatory drug, but it possessed poor skin permeation. In this context, polymeric nanoparticles have been used as an interesting and modern approach to improve drug efficacy, allowing sustainable distribution within the skin. Therefore, the objective of this study was to investigate the effect of meloxicam-loaded nanocapsules (M-NC) on the topical treatment of symptoms, inflammatory response and oxidative stress in an AD model in male BALB/c mice. 2, 4-Dinitrochlorobenzene (DNCB) (0.5 % in acetone/olive oil (3:1), 200 μl,) was applied to the dorsal skin of mice on experimental days 1-3 for sensitization. Mice were challenged with DNCB (1 %, 100 μl) on the dorsal skin (on days 14, 17, 20, 23, 26, and 29) and ear (right) (on days 14-29). Treatments with blank nanocapsules (B-NC), free meloxicam (M-F) or M-NC were applied to the backs of the mice from days 14 to 29. On the day 30, skin severity scores and scratching behavior were determined. After, animals were sacrificed and ears and dorsal skin were removed for determination of inflammatory parameters (edema, myeloperoxidase (MPO) activity) and oxidative parameters (thiobarbituric acid reactive species (TBARS) and non-protein thiol (NPSH) levels). Our results confirmed that DNCB increased the severity of skin lesions, scratching behavior, ear edema, ear MPO activity and dorsal skin TBARS levels in mice. An important finding of the present study was that topical application of M-NC was able to reverse skin severity scores, scratching behavior and inflammatory response induced by DNCB in mice, but did not have effect on the dorsal skin TBARS levels. B-NC or M-F treatments did not have effect in this model. Dorsal skin NPSH levels were not altered in any of the experimental groups. In summary, the data reported herein clearly demonstrated that meloxicam carried by polymeric nanocapsules the attenuate inflammatory response and subsequently ameliorated symptoms in a mouse model AD, while F-M treatment did not have effect.