Peptide Based Antibacterial Coating

描述(申请人提供)：该SBIR第一阶段项目的长期目标是开发用于医疗器械的抗菌涂料。在设备上使用传统抗菌剂对产生抗药性细菌构成巨大风险。其目标是开发一种以不同的作用模式工作的涂层，这种涂层不太可能支持耐药微生物的崛起。通过柔性系绳将抗菌肽Nisin连接到表面，将产生抗菌涂层。最近对这种多肽行为的研究表明，如果保持足够的溶剂可及性和分子流动性，当结合到表面时，可以保持抗菌活性。用这种方法制备的多肽涂层应该是安全的、功能性的和持久的。在第一阶段，化学修饰的多肽衍生物将共价结合到固定的端基活化的聚环氧乙烷链上。表面被拴住的乳链菌素的分布将被量化，游离和固定化的多肽-聚合物结构的抗菌性能将使用敏感的细菌指示菌株进行评估。在有血浆存在的情况下，将测量束缚多肽的稳定性和活性持续时间。在第二阶段，将在大鼠的中心静脉导管感染模型中测试涂层的活性，以对抗临床上重要的细菌菌株。这项研究将与俄勒冈州立大学密切合作，从而将成功所需的两项重要技术结合在一起。此次合作将把DV Bimed在表面涂层技术方面的工业研发经验与俄亥俄州立大学在抗菌肽方面的独特基础科学经验融为一体。这些涂层的商业应用包括：导管、医疗、光学和牙科设备以及研究抗菌肽活性的作用机制和结构要求的研究工具。 与医疗器械相关的感染是一个主要问题，需要抗菌涂层来防止疾病、发病率和额外成本。然而，目前的抗菌涂层支持耐药细菌的崛起，这是一个重要的医学问题。这项工作的目的是生产基于天然化合物的替代涂层，以杀灭细菌。这种化合物在医疗器械涂料中的使用有望为抗菌药物提供一种安全、有效的替代品，使其能够得到更广泛的使用。如果成功，这些涂层将通过降低患者患难治性感染的风险来改善患者护理，并将成为控制耐药细菌上升的努力中的一个重要里程碑。

DESCRIPTION (provided by applicant): The long-term objective of this SBIR Phase I project is to develop antibacterial coatings for medical devices. The use of traditional antimicrobials on devices poses a substantial risk for developing drug resistant bacteria. The objective is to develop coatings that work by a different mode of action that are not likely to support the rise of resistant microorganisms. Antibacterial coatings will be produced by linking an antibacterial peptide, nisin, to surfaces via a flexible tether. Recent studies of this peptide's behavior suggest antimicrobial activity could be maintained when bound to a surface if sufficient solvent accessibility and molecular mobility are preserved. A coating of the peptide prepared in this way should be safe, functional, and long-lasting. In Phase I, chemically-modified peptide derivatives will be covalently bound to immobilized, end-group activated poly(ethylene oxide) chains. The distribution of surface tethered nisin will be quantified, and antibacterial properties of free and immobilized peptide-polymer constructs will be evaluated using a sensitive indicator strain of bacteria. The stability and duration of activity of tethered peptides will be measured in the presence of plasma. In Phase II, coating activity will be tested against clinically significant bacteria strains and in a model of central venous catheter infection in rats. This research will be conducted in close cooperation with Oregon State University thereby bringing together two important technologies that will be required for success. The collaboration will assimilate the strength of DV Biomed's industrial R&D experience in surface coating technology with OSU's unique basic science experience with the antibacterial peptide. Commercial applications for these coatings include: catheters, medical, optical and dental devices as well as research tools to investigate the mechanism of action and structural requirements for activity of antibacterial peptides. Medical device-related infections are a major problem and antibacterial coatings are needed to prevent illness, morbidity and excess cost. However, current antibacterial coatings support the rise of drug resistant bacteria, which is an important medical concern. The aim of this work is to produce alternative coatings based on natural compounds that kill bacteria. The use of such compounds in medical device coatings is expected to provide a safe, effective alternative to antibacterial drugs that will enable broader use. If successful, these coatings will improve patient care by decreasing their risk for developing hard to treat infections and will be an important milestone in the effort to control the rise of drug resistant bacteria.