Institute of Materials Research and Engineering, 2 Fusionopolis Way, #08-03 Innovis, Singapore, 138634.
School of Materials Science and Engineering, College of Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798.
Macromol Biosci. 2019 Apr;19(4):e1800466. doi: 10.1002/mabi.201800466. Epub 2019 Jan 29.
Poly([R]-3-hydroxybutyrate) (PHB), a natural biodegradable polyester, has attracted much attention as a new biomaterial because of its sustainability and good biocompatibility. In this study, it is discovered that PHB can be conveniently functionalized to obtain a number of platform chain architectures that may provide a wide range of functional copolymers. In a transesterification reaction, linear (di-hydroxylated) and star shaped (tri- and tetra-hydroxylated) PHB oligomers are synthesized, followed by copolymerization with 2-(dimethylamino)ethyl methacrylate and quaternization with benzyl bromide to afford antimicrobial properties. The antimicrobial activities of the quaternary salts against clinically relevant pathogens on the interactions with outer and cytoplasmic membranes, lethal mechanisms, multipassage resistance, and synergy effect with antibiotics are investigated. Cationic PHB copolymers show effectiveness as antimicrobial agents, with minimum inhibitory concentration values 0.24-0.65 µm (or µmol dm ) (or 32-128 µg mL ) against Gram-positive and Gram-negative bacteria. Modifying the copolymer architectures into star shapes results in enhanced effectiveness to disrupt the membrane integrity. Synergistic effects are attained for all the quaternized PHB derivatives when they are used together with tobramycin. Multipassage resistance does not occur in both the linear and star derivatives against Gram-negative bacteria after 20 passages.
聚（R）-3-羟基丁酸酯（PHB）是一种天然可生物降解的聚酯，由于其可持续性和良好的生物相容性，作为一种新型生物材料引起了广泛关注。在这项研究中，人们发现 PHB 可以方便地进行功能化，得到许多平台链结构，这些结构可能提供广泛的功能性共聚物。在酯交换反应中，合成了线性（二羟化）和星形（三羟化和四羟化）PHB 低聚物，然后与 2-（二甲氨基）乙基甲基丙烯酸酯共聚，并与苄基溴季铵化，赋予其抗菌性能。研究了季铵盐与胞外和细胞质膜相互作用、致死机制、多代抗性以及与抗生素的协同作用对临床相关病原体的抗菌活性。阳离子 PHB 共聚物作为抗菌剂有效，对革兰氏阳性菌和革兰氏阴性菌的最小抑菌浓度值为 0.24-0.65 µm（或 µmol dm ）（或 32-128 µg mL ）。将共聚物结构修饰为星形结构会增强破坏膜完整性的效果。当与妥布霉素一起使用时，所有季铵化 PHB 衍生物都具有协同作用。在 20 次传代后，线性和星形衍生物对革兰氏阴性菌均未出现多代抗性。
