Efeito da aplicação local de curcumin nanoparticulado em modelo de doença periodontal experimental induzido por LPS
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Data
2016-12-07
Autores
Galvis Zambrano, Laura Melissa [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Curcumin é a denominação coletiva do composto extraído das raízes da planta herbácea Curcuma longa. A literatura reporta múltiplas atividades biológicas do curcumin, incluindo potente atividade anti-inflamatória. Estudos in vitro e in vivo demonstram que a administração de curcumin reduz a inflamação e destruição tecidual associadas à doença periodontal. No entanto, a maioria dos estudos in vivo administra o curcumin por via oral, o que pode limitar os efeitos deste composto devido à sua hidrofobicidade, baixa absorção no trato gastrointestinal e reduzida meia-vida plasmática. Estas limitações farmacodinâmicas induziram a busca de veículos alternativos para favorecer a biodisponibilidade e atividade biológica do curcumin. O presente estudo foi concebido como um trabalho de prova de princípio visando avaliar o efeito biológico da administração local de curcumin veiculado em nanopartículas, considerando a natureza sítio-específica da doença periodontal e as pobres propriedades farmacodinâmicas do curcumin. Dezesseis ratos Holtzman foram divididos em dois grupos de 8 animais, segundo a indução de doença periodontal experimental por meio de injeções bilaterais de LPS (3 µL, 10 mg/mL) ou do mesmo volume do veículo PBS (pH 7,4) como controle. Estas injeções foram realizadas no tecido gengival palatino adjacente aos primeiros molares superiores 3vezes/semana durante 4 semanas. Injeções de nanopartículas contendo curcumin (50 mg/mL, 3 µL/injeção) ou do mesmo volume do veículo de nanopartículas sem curcumin foram realizadas de forma contra-lateral (lado esquerdo: nanocurcumin, lado direito: veículo) nos mesmos sítios em todos os animais, 2vezes/semana durante as 4 semanas. A administração local do nanocurcumin reduziu a reabsorção óssea inflamatória, avaliada por µCT e por análise macroscópica. Esta redução foi acompanhada por significativa diminuição do número de osteoclastos e de células inflamatórias nos tecidos em que foi injetado LPS e nanocurcumin em comparação aos tecidos em que foi injetado LPS e veículo de nanopartículas. Também observamos marcante atenuação da ativação das vias de sinalização p38 MAPK e NF-kB nos tecidos gengivais injetados com o nanocurcumin. Conclui-se que a administração local de nanocurcumin veiculado em nanopartículas inibe a reabsorção óssea e a inflamação associadas ao modelo de doença periodontal induzido por injeções de LPS.
Curcumin is the collective denomination of the compound extracted from the rhizomes of Curcuma longa herbal plant. There is evidence indicating that curcumin has multiple biological activities, including potent anti-inflammatory properties. Both in vitro and in vivo studies demonstrate that curcumin may attenuate inflammation and the connective tissue destruction associated with periodontal disease. However, most of the in vivo studies uses an oral systemic administration route, which is limited by curcumin's hidrophobicity, poor absorption rate in the gastrointestinal tract and reduced half-life in the plasma. These pharmacodynamic limitations prompted the search for alternative vehicles to enhance the bioavailability and biological activity of curcumin. This proof of principle study was designed to assess the biological effect of the local administration of curcumin in a nanoparticle vehicle on experimental periodontal disease, considering the site-specific nature of periodontal disease and also the poor pharmacodynamic properties of curcumin. Sixteen 16 Holtzman rats were divided into two groups of 8 animals according to the induction of experimental periodontal disease by bilateral injections of LPS (3 µL of a 10mg/mL solution) or of the vehicle control (3 µL of PBS, pH 7.4) directly into the gingival tissues adjacent to the palatal aspect of the upper first molars 3time/week for 4 weeks. The same volume of curcumin-loaded nanoparticles (50 mg/mL) or of nanoparticle vehicle were injected into the same sites 2time/week. µCT and macroscopic analysis showed that local administration of curcumin inhibited inflammatory bone resorption. Histomorphometric analysis indicated a significant decrease in the number of osteoclasts and inflammatory cells in the diseased gingival tissues injected with nanocurcumin in comparison with the diseased gingival tissues injected with nanoparticle vehicle. Also, western blot analysis showed a marked attenuation in the activation of p38 MAPK and NF-kB. It is concluded that local administration of curcumin-loaded nanoparticles effectively inhibited inflammation and bone resorption associated with experimental periodontal disease.
Curcumin is the collective denomination of the compound extracted from the rhizomes of Curcuma longa herbal plant. There is evidence indicating that curcumin has multiple biological activities, including potent anti-inflammatory properties. Both in vitro and in vivo studies demonstrate that curcumin may attenuate inflammation and the connective tissue destruction associated with periodontal disease. However, most of the in vivo studies uses an oral systemic administration route, which is limited by curcumin's hidrophobicity, poor absorption rate in the gastrointestinal tract and reduced half-life in the plasma. These pharmacodynamic limitations prompted the search for alternative vehicles to enhance the bioavailability and biological activity of curcumin. This proof of principle study was designed to assess the biological effect of the local administration of curcumin in a nanoparticle vehicle on experimental periodontal disease, considering the site-specific nature of periodontal disease and also the poor pharmacodynamic properties of curcumin. Sixteen 16 Holtzman rats were divided into two groups of 8 animals according to the induction of experimental periodontal disease by bilateral injections of LPS (3 µL of a 10mg/mL solution) or of the vehicle control (3 µL of PBS, pH 7.4) directly into the gingival tissues adjacent to the palatal aspect of the upper first molars 3time/week for 4 weeks. The same volume of curcumin-loaded nanoparticles (50 mg/mL) or of nanoparticle vehicle were injected into the same sites 2time/week. µCT and macroscopic analysis showed that local administration of curcumin inhibited inflammatory bone resorption. Histomorphometric analysis indicated a significant decrease in the number of osteoclasts and inflammatory cells in the diseased gingival tissues injected with nanocurcumin in comparison with the diseased gingival tissues injected with nanoparticle vehicle. Also, western blot analysis showed a marked attenuation in the activation of p38 MAPK and NF-kB. It is concluded that local administration of curcumin-loaded nanoparticles effectively inhibited inflammation and bone resorption associated with experimental periodontal disease.
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Palavras-chave
Doenças periodontais, Curcumina, Inflamação, Reabsorção óssea, Periodontics diseases, Curcumin, Inflammation, Bone resorption