Peptide Based Antibacterial Coating

描述（由申请人提供）：这项工作的目标是开发双重功能的抗菌涂层，防止生物膜的形成和血栓。这项技术的一个关键特点是，它将防止生物膜的形成，而不会产生抗生素耐药细菌的相关风险。该涂层结合了一种新型的抗蛋白质聚合物和抗菌肽。这种肽通过多层机制杀死细菌，与临床抗生素的机制根本不同，因此不太可能促进耐药性。涂层将通过两种方式将肽结合到表面上：通过柔性系绳和包裹。用这种方法制备的抗菌肽层应具有安全性、功能性和长效性。该二期SBIR计划的重点是满足短期中心静脉导管的需求。首先，选择涂层成分以使活性最大化。活性和作用方式将被表征与密切关注共价系留与物理结合肽。作为这一过程的一部分，表面结合抗菌剂的结构和功能关系将被检查。其次，将开发方法来确保涂层在生理条件下的坚固性能。将在这些条件下测量随时间的疗效，其中疗效标准包括生物膜抑制以及非血栓形成性。然后将生产涂有这种技术的原型导管，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菌株。该计划将通过使用大鼠中心静脉导管感染模型对原型进行体内评估来完成。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.