IMMOBILIZATION OF ANTIMICROBIAL PEPTIDES

抗菌肽的固定化

• 批准号: 3506084
• 负责人: LISE W DURAN
• 金额: $ 23.99万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3506084
• 关键词: Escherichia coli; Staphylococcus; antibiotics; bacterial endocarditis; biomaterial development /preparation; catheterization; covalent bond; fibroblasts; high performance liquid chromatography; iatrogenic disease; laboratory mouse; laboratory rat; microorganism culture; peptides; photochemistry; prosthesis; radiotracer; slow release drug; tissue /cell culture

Each year, 850,000 cases of implant-related infections occur in the United States. Infection of catheters, orthopedic and dental prostheses, vascular grafts and valves, pacemaker leads, breast implants, and cerebrospinal fluid shunts can lead to re-operation, amputation, or death. The infectious organisms are either iatrogenically introduced during implantation or introduced post-surgery through septicemic routes. Administration of antibiotics is often an ineffective treatment; prevention is the most promising approach to decreasing device-associated septicemia. One approach to preventing bacterial colonization is by attaching antimicrobial agents to the device prior to implantation. During the Phase I project, we successfully derivatized, purified, and covalently immobilized antimicrobial peptides to model support matrices and performed preliminary assessments of the retained microbial activities. Proof-of-concept for this project was demonstrated by preparing modified surfaces that resist colonization of infectious organisms, as tested in vitro. In Phase II, we plan to optimize the chemistry and further explore the microbicidal activity of model substrate materials in vitro. In addition, a supplementary method for retardation of bacterial colonization involving a slow release mechanism of peptide will be explored. Bacterial colonization and toxicity testing will be performed on modified materials in vitro; toxicity and efficacy studies will be conducted in vivo.

在美国，每年发生85万例植入物相关感染。 States. 导管、整形外科和假牙、血管感染 移植物和瓣膜、起搏器电极导线、乳房植入物和脑脊液 液体分流可导致再次手术、截肢或死亡。 的 传染性微生物或者是医源性引入， 植入或通过败血症途径在术后引入。 使用抗生素通常是无效的治疗;预防 是减少器械相关败血症的最有前途的方法。 防止细菌定植的一种方法是将 在植入前，将抗菌剂注入器械。 在第一阶段项目中，我们成功地衍生，纯化， 将抗微生物肽共价固定到模型支持基质上， 对保留的微生物活性进行了初步评估。 该项目的概念验证是通过准备修改后的 抗感染性生物定殖的表面，如 体外 在第二阶段，我们计划优化化学成分， 模型基质材料的体外杀菌活性。 在 此外，还提供了一种延缓细菌定植的补充方法， 涉及肽的缓慢释放机制将被探索。 细菌 将对改性材料进行定殖和毒性试验 体外;毒性和疗效研究将在体内进行。