Post-Graduation Program in Oral Science, Department of Dentistry, UFRN, Natal 59072-970, Brazil.
Post-Graduation Program in Pharmacology/Post-Graduation Program in Morphology, Department of Morphology, UFC, Fortaleza 60440-900, Brazil.
Int J Mol Sci. 2018 Nov 6;19(11):3488. doi: 10.3390/ijms19113488.
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--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-1β and TNF-α levels were analyzed by ELISA immunoassay. Quantitative RT-PCR was used (, , , and ). The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm ( < 0.05) with a polydispersity index of 0.285 ( < 0.05), Z potential of 8.16 ± 1.1 mV ( < 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-1β and TNF-α ( < 0.05), increased expression gene ( < 0.05) and decreased , , and ( < 0.05). It is concluded that MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats.
证据表明,二甲双胍是一种降糖药物,可发挥良好的抗炎作用并减少骨质流失。将纳米粒用于二甲双胍可能有助于提高治疗效果。本研究旨在评估盐酸二甲双胍载聚(丙交酯-乙交酯)(PLGA)/(MET-载 PLGA)对糖尿病大鼠结扎诱导牙周炎模型的影响。采用平均粒径、粒径、多分散指数和包封效率对 MET-载 PLGA 进行了表征。使用 Microcomputed Tomography(µCT)和组织病理学及免疫组织化学分析对上颌进行扫描。通过 ELISA 免疫测定分析 IL-1β 和 TNF-α 水平。采用定量 RT-PCR( , , , )。MET-载 PLGA 纳米粒的平均粒径为 457.1 ± 48.9nm( < 0.05),多分散指数为 0.285( < 0.05),Z 电位为 8.16 ± 1.1mV( < 0.01),包封效率(EE)为 66.7 ± 3.73。MET-载 PLGA 10mg/kg 治疗组炎症细胞较少,RANKL、组织蛋白酶 K、OPG 和骨钙素染色较弱,IL-1β 和 TNF-α 水平降低( < 0.05), 表达基因增加( < 0.05), 、 、 降低( < 0.05)。结论:MET-载 PLGA 可减少糖尿病大鼠牙周炎的炎症和骨质流失。