Institute of Biomaterials and Biomedical Engineering, University of Toronto, Ontario, Canada.
Division of Engineering Science, University of Toronto, Ontario, Canada.
Dent Mater. 2019 Feb;35(2):229-243. doi: 10.1016/j.dental.2018.11.016. Epub 2018 Nov 29.
Antimicrobial oligomers synthesized from ciprofloxacin (CF) and metronidazole (MN) were investigated for their potential use in dental adhesives.
Susceptibility of the cariogenic bacterium Streptococcus mutans UA159 to CF, MN, and CF/MN combination was evaluated. Hydrolytic stability and drug release from the oligomers was studied in buffer and simulated human salivary esterase conditions. Cytotoxicity of films with 15wt% drug oligomers co-polymerized with commercial monomers were assessed using human gingival fibroblasts (HGFs). In-house adhesives were prepared and characterized for viscosity. Polymerized films were analysed for gel content and water swelling. Interfacial fracture toughness (K) of composites bonded to dentin by either a 2 or 3-step etch-and-rinse approach using the in-house formulated adhesives was measured.
The respective minimum inhibitory concentration for CF and MN against S. mutans was 0.7 and 2400μg/mL, with the combination having an additive effect (0.35μg/mL CF with 1200μg/mL MN). Antibiotics were released upon hydrolysis of the oligomers. Films containing the drug oligomers were not cytotoxic against HGFs. Replacing 2-hydroxyethyl methacrylate with the drug oligomers increased the viscosity of the experimental adhesives, reduced gel content, and decreased swelling of films in water. Antimicrobial adhesives demonstrated bonding to dentin with interfacial K values comparable to the in-house control in the 2-step application, and with slightly lower K values in the 3-step approach.
The antimicrobial oligomers can be incorporated into dental adhesive systems using formulations that show comparable fracture toughness to commercial materials, and may provide a means to deliver local antimicrobial drug release at the marginal interface.
研究了由环丙沙星 (CF) 和甲硝唑 (MN) 合成的抗菌低聚物，以评估其在牙科胶粘剂中的潜在用途。
评估了致龋菌变异链球菌 UA159 对 CF、MN 和 CF/MN 组合的敏感性。在缓冲液和模拟人唾液酯酶条件下研究了低聚物的水解稳定性和药物释放。用含 15wt%药物低聚物与商业单体共聚的薄膜评估了细胞毒性。用人牙龈成纤维细胞 (HGFs) 评估了用自制胶粘剂制备的粘性。聚合物薄膜的凝胶含量和水膨胀用分析。用自制的胶粘剂，通过两步或三步酸蚀-冲洗法将复合材料粘接在牙本质上，测量复合材料的界面断裂韧性 (K)。
CF 和 MN 对 S. mutans 的最低抑菌浓度分别为 0.7 和 2400μg/mL，组合具有相加作用 (0.35μg/mL CF 与 1200μg/mL MN)。抗生素通过低聚物的水解而释放。含有药物低聚物的薄膜对 HGFs 无细胞毒性。用药物低聚物替代 2-羟乙基甲基丙烯酸酯会增加实验性胶粘剂的粘度，降低凝胶含量，减少薄膜在水中的膨胀。抗菌胶粘剂显示与牙本质的粘接，在两步应用中，其界面 K 值与自制对照物相当，而在三步应用中，其 K 值略低。
可以将抗菌低聚物纳入牙科胶粘剂系统中，使用的配方显示出与商业材料相当的断裂韧性，并且可以提供在边缘界面局部释放抗菌药物的手段。
