Zhang Ziwen, Jones Megan M, Sabatini Camila, Vanyo Stephen T, Yang Ming, Kumar Abhishek, Jiang Yancheng, Swihart Mark T, Visser Michelle B, Cheng Chong
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, USA.
Biomater Sci. 2021 Mar 21;9(6):2043-2052. doi: 10.1039/d0bm01910k. Epub 2021 Jan 19.
This work reports on polymer-antibiotic conjugates (PACs) as additives to resin-based restorative dental materials as a new strategy to convey sustained antibacterial character to these materials. Such antibacterial performance is expected to improve their longevity in the oral cavity. Using the previously reported ciprofloxacin (Cip)-based PAC as a control, a penicillin V (PV)-based PAC was investigated. The monomer-antibiotic conjugate (MAC) containing a methacrylate monomer group and a PV moiety was prepared via nucleophilic substitution between 2-chloroethyl methacrylate (CEMA) and penicillin V potassium (PVK). The PV-based PAC was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of the MAC with hydroxyethyl methacrylate (HEMA), and further characterized by H NMR and gel permeation chromatography (GPC) analysis. Antibiotic resistance was investigated by passaging bacteria in low concentrations of the antibiotic for 19 days, followed by a 48 h challenge at higher concentrations. Our results suggest that the development of antibiotic resistance is unlikely. Zone of inhibition (ZOI) assays revealed no clearing zones around PV-containing resins indicating minimal antibiotic leakage from the material. Similarly, MTT assay demonstrated that the antibiotic-containing specimens did not release cytotoxic byproducts that may inhibit human gingival fibroblast growth. Counting of colony-forming units in an S. mutans biofilm model was used to assess bacterial survival at baseline and after subjecting the antibiotic-containing resin specimens to an enzymatic challenge for 30 days. Significantly reduced bacterial counts were observed as the biofilm aged from 24 to 72 h, and salivary enzymatic exposure did not reduce the antibacterial efficacy of the discs, suggesting that PV-resin will be effective in reducing the re-incidence of dental caries.
本研究报道了将聚合物 - 抗生素共轭物（PACs）作为树脂基牙科修复材料的添加剂，作为赋予这些材料持续抗菌特性的新策略。预期这种抗菌性能会提高它们在口腔中的使用寿命。以先前报道的基于环丙沙星（Cip）的PAC作为对照，对基于青霉素V（PV）的PAC进行了研究。通过甲基丙烯酸2 - 氯乙酯（CEMA）与青霉素V钾（PVK）之间的亲核取代反应制备了含有甲基丙烯酸酯单体基团和PV部分的单体 - 抗生素共轭物（MAC）。基于PV的PAC通过MAC与甲基丙烯酸羟乙酯（HEMA）的可逆加成 - 断裂链转移（RAFT）聚合反应合成，并通过核磁共振氢谱（H NMR）和凝胶渗透色谱（GPC）分析进一步表征。通过在低浓度抗生素中传代细菌19天，然后在高浓度下进行48小时挑战来研究抗生素抗性。我们的结果表明不太可能产生抗生素抗性。抑菌圈（ZOI）试验显示含PV的树脂周围没有清晰区域，表明材料中抗生素泄漏极少。同样，MTT试验表明含抗生素的标本不会释放可能抑制人牙龈成纤维细胞生长的细胞毒性副产物。在变形链球菌生物膜模型中对菌落形成单位进行计数，以评估基线时以及含抗生素的树脂标本在酶攻击30天后的细菌存活情况。随着生物膜从24小时老化到72小时，观察到细菌数量显著减少，并且唾液酶暴露并未降低圆盘的抗菌效果，这表明PV树脂在降低龋齿复发率方面将是有效的。
