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Int J Mol Sci ; 19(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404181

RESUMO

Evidence shows that metformin is an antidiabetic drug, which can exert favorable anti-inflammatory effects and decreased bone loss. The development of nanoparticles for metformin might be useful for increased therapeutic efficacy. The aim of this study was to evaluate the effect of metformin hydrochloride-loaded Poly (d,l-Lactide-co-glycolide) (PLGA)/(MET-loaded PLGA) on a ligature-induced periodontitis model in diabetic rats. MET-loaded PLGA were characterized by mean diameter, particle size, polydispensity index, and entrapment efficiency. Maxillae were scanned using Microcomputed Tomography (µCT) and histopathological and immunohistochemical analysis. IL-1ß and TNF-α levels were analyzed by ELISA immunoassay. Quantitative RT-PCR was used (AMPK, NF-κB p65, HMGB1, and TAK-1). The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm (p < 0.05) with a polydispersity index of 0.285 (p < 0.05), Z potential of 8.16 ± 1.1 mV (p < 0.01), and entrapment efficiency (EE) of 66.7 ± 3.73. Treatment with MET-loaded PLGA 10 mg/kg showed low inflammatory cells, weak staining by RANKL, cathepsin K, OPG, and osteocalcin, and levels of IL-1ß and TNF-α (p < 0.05), increased AMPK expression gene (p < 0.05) and decreased NF-κB p65, HMGB1, and TAK-1 (p < 0.05). It is concluded that MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats.


Assuntos
Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Imuno-Histoquímica , Microscopia de Força Atômica , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Doenças Periodontais/diagnóstico , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/etiologia , Doenças Periodontais/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Microtomografia por Raio-X
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