Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Acta Biomater. 2015 Aug;22:131-40. doi: 10.1016/j.actbio.2015.04.023. Epub 2015 Apr 25.
Microbial biofilms are known to support a number of human infections, including those related to medical devices. This work is focused on the development of novel dual-function amphiphilic random copolymers to be employed as coatings for medical devices. Particularly, copolymers were obtained by polymerization of an antimicrobial cationic monomer (bearing tertiary amine) and an antioxidant and antimicrobial hydrophobic monomer (containing hydroxytyrosol, HTy). To obtain copolymers with various amphiphilic balance, different molar ratios of the two monomers were used. (1)H NMR and DSC analyses evidenced that HTy aromatic rings are able to interact with each other leading to a supra-macromolecular re-arrangement and decrease the copolymer size in water. All copolymers showed good antioxidant activity and Fe(2+) chelating ability. Cytotoxicity and hemolytic tests evidenced that the amphiphilic balance, cationic charge density and polymer size in solution are key determinants for polymer biocompatibility. As for the antimicrobial properties, the lowest minimal inhibitory concentration (MIC = 40 μg/mL) against Staphylococcus epidermidis was shown by the water-soluble copolymer having the highest HTy molar content (0.3). This copolymer layered onto catheter surfaces was also able to prevent staphylococcal adhesion. This approach permits not only prevention of biofilm infections but also reduction of the risk of emergence of drug-resistant bacteria. Indeed, the combination of two active compounds in the same polymer can provide a synergistic action against biofilms and suppress reactive species oxygen (ROS), known to promote the occurrence of antibiotic resistance.
微生物生物膜已知可以支持多种人类感染，包括与医疗器械相关的感染。这项工作专注于开发新型双功能两亲性无规共聚物，用作医疗器械的涂层。特别是，通过聚合抗菌阳离子单体（带有叔胺）和抗氧化和抗菌疏水性单体（含有羟基酪醇，HTy）来获得共聚物。为了获得具有不同两亲平衡的共聚物，使用了两种单体的不同摩尔比。（1）H NMR 和 DSC 分析表明，HTy 芳环能够相互作用，导致超分子重新排列，并降低共聚物在水中的尺寸。所有共聚物均表现出良好的抗氧化活性和 Fe（2+）螯合能力。细胞毒性和溶血试验表明，两亲平衡、阳离子电荷密度和溶液中聚合物的大小是聚合物生物相容性的关键决定因素。就抗菌性能而言，具有最高 HTy 摩尔含量（0.3）的水溶性共聚物对表皮葡萄球菌显示出最低的最小抑菌浓度（MIC = 40 μg/mL）。该共聚物层压在导管表面上也能够防止葡萄球菌的粘附。这种方法不仅可以预防生物膜感染，还可以降低出现耐药菌的风险。事实上，两种活性化合物在同一聚合物中的组合可以对生物膜产生协同作用，并抑制活性氧（ROS），已知 ROS 会促进抗生素耐药性的发生。
