Impacto da aplicação tópica do curcumin nanoparticulado no tratamento de lesões de líquen plano oral (LPO).
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2020-05-01
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Universidade Estadual Paulista (Unesp)
Resumo
Curcumin é um composto ativo derivado da planta Curcuma longa que exibe uma variedade de atividades biológicas. Inúmeros estudos têm documentado seu potencial anti-inflamatório e imunomodulatório, que pode ser associado ao tratamento de uma série de condições, como doenças inflamatórias intestinais, artrite reumatoide, câncer, diabetes, periodontite, bem como no tratamento de lesões de líquen plano oral (LPO). LPO é uma doença autoimune, mediada por células T e caracterizada pelo aparecimento de lesões nos tecidos orais, geralmente associada a sintomatologia dolorosa e com potencial de malignidade de 0,4% a 5%. Inúmeras pesquisas têm sido conduzidas com objetivo de determinar um tratamento eficaz e seguro para a doença, mas até o momento não há um protocolo padrão. O uso de corticosteroides tem sido a modalidade de tratamento mais indicada, entretanto, a necessidade de utilização destes fármacos por longos períodos e em altas doses podem provocar imunossupressão da cavidade oral. A literatura tem mostrado benefícios do curcumin sobre a redução dos sinais e sintomas da doença, além da ausência de toxicidade, mas a baixa biodisponibilidade do composto parece limitar sua efetividade clínica. Sua veiculação em nanopartículas tem sido uma das estratégias utilizadas para melhorar as características farmacológicas do composto e potencializar seus efeitos biológicos. Nesse estudo, propomos avaliar o potencial da aplicação tópica do curcumin nanoparticulado sobre a redução de sinais e sintomas do LPO, e investigar sua influência sobre o infiltrado inflamatório, a expressão dos subtipos de células T e ativação do fator de transcrição NF-ҝB. Pacientes receberam a aplicação local do curcumin nanoparticulado 0,5%, ou da nanopartícula vazia (veículo) três vezes ao dia, diariamente, durante 30 dias. Biopsias das lesões obtidas no baseline e ao final do tratamento foram utilizadas para avaliar a proporção e perfil de células T (CD3+, CD4+, CD8+, CD45+), bem como a ativação de NF-ԟB por imuno-histoquímica. Sinais clínicos das lesões foram avaliados utilizando a Classificação de Thongprasom, e a sintomatologia analisada segundo a escala visual analógica (VAS), semanalmente durante o período de aplicação dos compostos, e reavaliados 7, 30 e 60 dias após o término do tratamento. Curcumin reduziu acentuadamente a sintomatologia dos pacientes em todos os períodos analisados durante o tratamento (p<0.05), e apresentou ainda um efeito residual durante todo o período de reavaliação. Os sinais clínicos não foram alterados em nenhum dos grupos. A análise imuno-histoquímica demonstrou uma redução significativa das células T (CD3+, CD4+, CD8+ e CD45+) nas lesões tratadas com curcumin, especialmente das células T CD4+, mas sem modulação na ativação de NF- kappa B (p = 0,2).
Curcumin is an active compound derived from the Curcuma longa plant that exhibits a variety of biological activities. Numerous studies have documented its anti-inflammatory and immunomodulatory potential, which can be associated with the treatment of a number of conditions, such as inflammatory bowel diseases, rheumatoid arthritis, cancer, diabetes, periodontitis, as well as in the treatment of oral lichen planus lesions (OLP). OLP is an autoimmune disease, mediated by T cells and characterized by the appearance of lesions in the oral tissues, usually associated with painful symptoms and with a malignant potential of 0.4% to 5%. Countless research have been conducted with the objective of determining an effective and safe treatment for the disease, but so far there is no standard protocol. The use of corticosteroids has been the most indicated treatment modality, however, the need to use these drugs for long periods and in high doses can cause immunosuppression of the oral cavity. The literature has shown benefits of curcumin on reducing signs and symptoms of the disease, in addition to the absence of toxicity, but the low bioavailability of the compound seems to limit its clinical effectiveness. Its delivery in nanoparticles has been one of the strategies used to improve the pharmacological characteristics of the compound and enhance its biological effects. In this study, we propose to evaluate the potential of topical application of curcumin -loaded nanoparticle on the reduction of signs and symptoms of OLP, and to investigate its influence on inflammatory infiltrate, the expression of T cell subtypes and the activation of NF-ҝB transcription factor. Patients apply locally 0.5% nanoparticulate curcumin, or empty nanoparticle (vehicle) three times a day, daily, for 30 days. Biopsies of the lesions obtained at the baseline and at the end of treatment were used to assess the proportion and profile of T cells (CD3 +, CD4 +, CD8 +, CD45 +), as well as the activation of the NF-ԟB transcription factor by immunohistochemistry. Clinical signs of the lesions were evaluated using the Thongprasom Score, and the symptoms analyzed according to the visual analog scale (VAS), weekly during the period of application of the compounds, and reassessed 7, 30 and 60 days after the end of treatment. Curcumin markedly reduced the symptoms of patients in all periods analyzed during treatment (p <0.05) and presented a residual effect throughout the reassessment period. The clinical signs were not changed in any of the groups. Immunohistochemical analysis demonstrated a significant reduction in (CD3 +, CD4 +, CD8 + and CD45 +) T cells in lesions treated with curcumin, especially CD4 + T cells, but no modulation in activation of NF- kappa B expression (p = 0.2).
Curcumin is an active compound derived from the Curcuma longa plant that exhibits a variety of biological activities. Numerous studies have documented its anti-inflammatory and immunomodulatory potential, which can be associated with the treatment of a number of conditions, such as inflammatory bowel diseases, rheumatoid arthritis, cancer, diabetes, periodontitis, as well as in the treatment of oral lichen planus lesions (OLP). OLP is an autoimmune disease, mediated by T cells and characterized by the appearance of lesions in the oral tissues, usually associated with painful symptoms and with a malignant potential of 0.4% to 5%. Countless research have been conducted with the objective of determining an effective and safe treatment for the disease, but so far there is no standard protocol. The use of corticosteroids has been the most indicated treatment modality, however, the need to use these drugs for long periods and in high doses can cause immunosuppression of the oral cavity. The literature has shown benefits of curcumin on reducing signs and symptoms of the disease, in addition to the absence of toxicity, but the low bioavailability of the compound seems to limit its clinical effectiveness. Its delivery in nanoparticles has been one of the strategies used to improve the pharmacological characteristics of the compound and enhance its biological effects. In this study, we propose to evaluate the potential of topical application of curcumin -loaded nanoparticle on the reduction of signs and symptoms of OLP, and to investigate its influence on inflammatory infiltrate, the expression of T cell subtypes and the activation of NF-ҝB transcription factor. Patients apply locally 0.5% nanoparticulate curcumin, or empty nanoparticle (vehicle) three times a day, daily, for 30 days. Biopsies of the lesions obtained at the baseline and at the end of treatment were used to assess the proportion and profile of T cells (CD3 +, CD4 +, CD8 +, CD45 +), as well as the activation of the NF-ԟB transcription factor by immunohistochemistry. Clinical signs of the lesions were evaluated using the Thongprasom Score, and the symptoms analyzed according to the visual analog scale (VAS), weekly during the period of application of the compounds, and reassessed 7, 30 and 60 days after the end of treatment. Curcumin markedly reduced the symptoms of patients in all periods analyzed during treatment (p <0.05) and presented a residual effect throughout the reassessment period. The clinical signs were not changed in any of the groups. Immunohistochemical analysis demonstrated a significant reduction in (CD3 +, CD4 +, CD8 + and CD45 +) T cells in lesions treated with curcumin, especially CD4 + T cells, but no modulation in activation of NF- kappa B expression (p = 0.2).
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Palavras-chave
Líquen plano oral, Curcumin, Nanopartículas, Linfócitos, NF-kappa B, Ensaios Clínicos, Oral lichen planus, Clinical trials, Curcumin, Nanoparticles, Lymphocytes, NFkappa B