Peptide Based Antibacterial Coating

描述(申请人提供)：这项工作的目标是开发双功能抗菌涂层，防止生物膜形成和血栓形成。这项技术的一个关键特征是，它将防止生物膜的形成，而不会产生产生抗生素耐药性细菌的相关风险。该涂层将一种新型的抗蛋白质聚合物与抗菌肽结合在一起。这种多肽通过一种与临床抗生素根本不同的多层机制杀死细菌，因此不太可能促进耐药性。涂层将通过两种方式将多肽结合到表面：通过柔性系绳和包埋法。用这种方法制备的一层抗菌肽应该是安全的、功能性的和持久的。这项第二阶段的SBIR计划侧重于满足短期中心静脉导管的要求。首先，将选择涂层成分以最大限度地提高活性。活性和作用模式将通过仔细观察共价结合的多肽和物理结合的多肽来表征。作为这一过程的一部分，将研究表面结合抗菌剂的结构和功能关系。第二，将开发确保涂层在生理条件下的坚固性能的方法。将测量在这些条件下随着时间的推移的疗效，其中疗效标准包括生物膜抑制以及非血栓形成。然后，将生产涂有这项技术的原型导管，并对临床相关细菌进行测试，包括耐甲氧西林的金黄色葡萄球菌和表皮葡萄球菌。该计划将完成，并使用大鼠中心静脉导管感染模型对原型进行体内评估。商业应用包括导管、医疗、光学和牙科设备。

DESCRIPTION (provided by applicant): The objective of this work is to develop dual function antibacterial coatings that prevent biofilm formation and thrombus. A key feature of this technology is that it will prevent biofilm formation without an associated risk of creating antibiotic resistant bacteria. The coating combines a novel protein resistant polymer with an antibacterial peptide. The peptide kills bacteria through a multi- tiered mechanism that is fundamentally different from that of clinical antibiotics and is therefore unlikely to promote resistance. Coatings will be produced by binding the peptide to surfaces in two modes: via a flexible tether and entrapment. A layer of the antibacterial peptide prepared in this way should be safe, functional, and long-lasting. This Phase II SBIR plan focuses on meeting requirements for short term central venous catheters. First, coating constituents will be selected to maximize activity. Activity and mode of action will be characterized with a close look at covalently tethered versus physically bound peptides. As a part of this process, structural and functional relationships of surface bound antimicrobials will be examined. Second, methods will be developed to ensure robust performance of coatings under physiological conditions. Efficacy over time under these conditions will be measured, where efficacy criteria include biofilm inhibition as well as nonthrombogenicity. Prototype catheters coated with this technology will then be produced and tested against clinically relevant bacteria including methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. The plan will be completed with an in vivo evaluation of prototypes using a model of central venous catheter infection in rats. Commercial applications include catheters, medical, optical and dental devices.