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负载百里香酚或香芹酚的UiO-66的抗菌、抗炎和促骨能力评估

Evaluation of the Antibacterial, Anti-Inflammatory, And Bone-Promoting Capacity of UiO-66 Loaded with Thymol or Carvacrol.

作者信息

Zheng Minghe, Huang Yanlin, Hu Weiwei, Li Ru, Wang Jiaye, Han Mingfang, Li Zehui

机构信息

Stomatology Center of Hangzhou Normal University Affiliated Hospital The Chinese Hospital of China, Hangzhou 310015, Zhejiang Province, People's Republic of China.

Hangzhou Normal University, The Chinese University of China, Hangzhou 310015, Zhejiang Province, People's Republic of China.

出版信息

ACS Appl Mater Interfaces. 2024 Jul 17;16(28):36017-36029. doi: 10.1021/acsami.4c04139. Epub 2024 Jul 8.

Abstract

Oral infectious diseases have a significant impact on the health of oral and maxillofacial regions, as well as the overall well-being of individuals. Carvacrol and thymol, two isomers known for their effective antibacterial and anti-inflammatory properties, have gained considerable attention in the treatment of oral infectious diseases. However, their application as topical drugs for oral use is limited due to their poor physical and chemical stability. UiO-66, a metal-organic framework based on zirconium ion (Zr4+), exhibits high drug loading capability. Carvacrol and thymol were efficiently loaded onto UiO-66 with loading rates of 79.60 ± 0.71% and 79.65 ± 0.76%, respectively. The release rates of carvacrol and thymol were 77.82 ± 0.87% and 76.51 ± 0.58%, respectively, after a period of 72 h. Moreover, Car@UiO-66 and Thy@UiO-66 demonstrated excellent antibacterial properties against Candida albicans, Escherichia coli, and Staphylococcus aureus with minimum bactericidal concentrations (MBC) of 0.313 mg/mL, 0.313 mg/mL, and 1.25 mg/mL, respectively. Furthermore, based on the results of the CCK8 cytotoxicity assay, even at concentrations as high as 1.25 mg/mL, Car@UiO-66 and Thy@UiO-66 exhibited excellent biocompatibility with a relative cell survival rate above 50%. These findings suggest that Car@UiO-66 and Thy@UiO-66 possess favorable biocompatibility properties without significant toxicity towards periodontal membrane cells. Additionally, in vivo studies confirmed the efficacy of Car@UiO-66and Thy@UiO-66 in reducing inflammation, promoting bone formation through inhibition of TNF-a and IL6 expression, enhancement of IL10 expression, and acceleration of bone defect healing. Therefore, the unique combination of antibacterial, anti-inflammatory, and osteogenic properties make Car@UiO-66 and Thy@Ui O-66 promising candidates for the treatment of oral infectious diseases and repairing bone defects.

摘要

口腔感染性疾病对口腔颌面部健康以及个体的整体健康有着重大影响。香芹酚和百里酚这两种同分异构体以其有效的抗菌和抗炎特性而闻名,在口腔感染性疾病的治疗中受到了广泛关注。然而,由于它们较差的物理和化学稳定性,其作为口腔局部用药的应用受到限制。UiO - 66是一种基于锆离子(Zr4+)的金属有机框架材料,具有较高的载药能力。香芹酚和百里酚分别以79.60±0.71%和79.65±0.76%的载药率高效负载到UiO - 66上。经过72小时后,香芹酚和百里酚的释放率分别为77.82±0.87%和76.51±0.58%。此外,Car@UiO - 66和Thy@UiO - 66对白色念珠菌、大肠杆菌和金黄色葡萄球菌表现出优异的抗菌性能,其最小杀菌浓度(MBC)分别为0.313mg/mL、0.313mg/mL和1.25mg/mL。此外,基于CCK8细胞毒性试验结果,即使在高达1.25mg/mL的浓度下,Car@UiO - 66和Thy@UiO - 66仍表现出优异的生物相容性,相对细胞存活率高于50%。这些发现表明,Car@UiO - 66和Thy@UiO - 66具有良好的生物相容性,对牙周膜细胞无明显毒性。此外,体内研究证实了Car@UiO - 66和Thy@UiO - 66在减轻炎症、通过抑制TNF - a和IL6表达促进骨形成、增强IL10表达以及加速骨缺损愈合方面的功效。因此,抗菌、抗炎和成骨特性的独特组合使Car@UiO - 66和Thy@UiO - 66成为治疗口腔感染性疾病和修复骨缺损的有前途的候选药物。

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