Peptide Based Antibacterial Coating

肽基抗菌涂层

• 批准号: 7329644
• 负责人: Jennifer Ann Neff
• 金额: $ 39.82万
• 依托单位: ALLVIVO VASCULAR, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329644
• 关键词: Adsorption; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bacteria; Binding; Blood Proteins; Blood Vessels; Catheters; Charge; Clinical; Clinical Trials; Condition; Coupled; Crosslinker; Dental; Devices; Effectiveness; Electrostatics; Ensure; Evaluation; Goals; Government; Gram-Negative Bacteria; Gram-Positive Bacteria; Heating; Hemolysis; Human; In Vitro; Industrial Product; Infection; Infection prevention; Lead; Licensing; Marketing; Measures; Medical; Medical Device; Methicillin Resistance; Methods; Microbial Biofilms; Modeling; Nisin; Nitrilotriacetic Acid; Object Attachment; Optics; Oxides; PEO-PPO-PEO; Pediococcus; Peptides; Performance; Persons; Phase; Physiological; Polyethylene Glycols; Polymers; Polypropylenes; Polyurethanes; Preclinical Testing; Process; Production; Property; Proteins; Purpose; Rattus; Relative (related person); Resistance; Risk; Sales; Serum; Services; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Staging; Staphylococcus aureus; Staphylococcus epidermidis; Surface; Technology; Testing; Thrombus; Time; Venous; Work; antimicrobial; base; clinically relevant; clinically significant; commercial application; commercialization; copolymer; cost effective; day; implantation; in vivo; irradiation; killings; novel; prevent; programs; prototype; research and development; sound; surfactant

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.

描述（由申请人提供）：这项工作的目的是开发防止生物膜形成和血栓的双功能抗菌涂层。这项技术的一个关键特征是，它将防止生物膜形成，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一种抗菌肽。该肽通过多层次机制杀死细菌，这与临床抗生素的机制有根本不同，因此不太可能促进耐药性。将通过以两种模式将肽结合到表面来产生涂层：通过柔性系链和包埋。以这种方式制备的抗菌肽层应该是安全的、功能性的、持久的。本阶段II SBIR计划重点关注满足短期中心静脉导管的要求。首先，将选择涂层成分以使活性最大化。活性和作用模式将通过仔细观察共价连接的肽与物理结合的肽来表征。作为该过程的一部分，将检查表面结合的抗菌剂的结构和功能关系。其次，将开发方法以确保涂层在生理条件下的稳健性能。将测量在这些条件下随时间推移的疗效，其中疗效标准包括生物膜抑制以及无血栓形成。然后将生产涂有该技术的原型导管，并针对临床相关细菌进行测试，包括耐甲氧西林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价来完成。商业应用包括导管、医疗、光学和牙科设备。