Peptide-mediated Attachment of Drug-loaded Microparticles to Medical Devices

肽介导的载药微粒与医疗器械的附着

• 批准号: 7742051
• 负责人: JONATHAN A HODGES
• 金额: $ 30.94万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7742051
• 关键词: Address; Affinity; Anesthetics; Antibiotics; Area; Bacterial Infections; Binding; Biocompatible Materials; Biological; Biological Assay; Cardiac Surgery procedures; Cells; Ceramics; Chemistry; Clinical; Collection; Complication; Data; Development; Devices; Disinfection; Drug Delivery Systems; Drug Kinetics; Elderly; Ensure; Funding; Future; Glycolates; Goals; Healthcare Systems; Immunocompromised Host; Infection; Infection prevention; Lead; Length of Stay; Liquid substance; Local Anesthetics; Mediastinitis; Mediating; Medical Device; Metals; Microbial Biofilms; Modification; Motivation; Operative Surgical Procedures; Patients; Peptide Antibiotics; Peptides; Phage Display; Pharmaceutical Preparations; Phase; Physicians; Polyesters; Polymers; Postoperative Pain; Postoperative Period; Preparation; Process; Proteins; Repeat Surgery; Reporting; Research; Research Contracts; Risk; Safety; Site; Skin; Small Business Innovation Research Grant; Smoker; Societies; Solutions; Specificity; Sternotomy; Sternum; Surface; Surgical wound; System; Techniques; Technology; Teflon; Testing; Therapeutic; Tissues; To specify; United States; antimicrobial; aqueous; base; biomaterial compatibility; combat; commercialization; cost; design; diabetic; flexibility; improved; in vitro testing; in vivo; innovation; interfacial; microbial colonization; microbicide; mortality; new technology; novel; novel strategies; novel therapeutic intervention; point of care; prevent; programs; prophylactic; protein aminoacid sequence; psychologic; public health relevance; synthetic peptide

DESCRIPTION (provided by applicant): Mediastinitis is a common and sometimes devastating complication following open heart surgery. Despite the use of prophylactic systemic antibiotics and improved surgical techniques, bacterial infection remains a serious complication following almost all surgical procedures including median sternotomy. When surgical site infections occur, they can be devastating with immense financial and psychological costs especially in at-risk patients such as diabetics, smokers, the elderly, and immunocompromised. New technologies that prevent microbial colonization of the at-risk tissues in a surgical site could clearly benefit society by decreasing infection rates. The need for further innovation in the local delivery of antibiotics is our motivation to develop a peptide-mediated system to attach drug-loaded microparticles to medical devices. Affinergy is developing bifunctional affinity peptides, called interfacial biomaterials (IFBMs), that promote the attachment and retention of drugs, proteins, and cells on the surface of medical devices. Using phage display, we have identified specific peptide sequences that bind with high affinity to a number of materials and biologics. Synthesizing a pair of these peptides as a single IFBM promotes the attachment of drug, protein, or cell directly to the surface of a medical device. While we have observed promising preliminary data with this technique using antibiotics, peptide-mediated coating of medical devices with drug loaded microparticles may hold additional advantages. There are likely additional drugs and additional medical devices we might target with this novel microparticle-coating strategy. Because there exist such a wide range of potential peptide-microparticle device combinations, in this proposal we will focus on the development of a microparticle coating for sternal wires to prevent mediastinitis. Therefore, the goal of this Phase I research plan is to first optimize drug loaded poly (lactic-co-glycolic acid) (PLGA) microparticle preparations at Affinergy. We will then characterize and optimize candidate PLGA: metal IFBMs. Finally, we will examine the antimicrobial efficacy and biocompatibility of IFBM targeted microparticles, determining if the microparticles increase the potential of Affinergy device coating technology. The aims presented here represent a proof-of-principle research program, which would be expanded to include new antibiotics and commercialization strategies during a subsequent Phase II funding period. In the future, microparticles: medical device IFBMs could be used to attach microparticles loaded with a wide variety of therapeutic molecules from antibiotics to prevent post-operative infection to local anesthetics to treat post- operative pain. PUBLIC HEALTH RELEVANCE: Post-operative infection is a common and sometimes devastating complication following open heart surgery. Despite the use of prophylactic systemic antibiotics and improved surgical techniques, infection remains a serious complication. The need for further innovation in localized antibiotic delivery is our motivation to develop a peptide-mediated attachment system for drug-loaded microparticles onto medical devices. Affinergy is developing bifunctional affinity peptides, called interfacial biomaterials (IFBMs), that promote the attachment and retention of drugs, proteins, and cells on the surface of medical devices. While we have observed promising preliminary data with this technique using antibiotics, peptide-mediated coating of medical devices with drug loaded microparticles may hold additional advantages. There are likely additional drugs and additional medical devices we might target with this novel microparticle coating strategy. In this proposal we focus on the development of a microparticle coating for sternal wires to deliver antibiotics locally following open heart surgery. In the future, microparticle: medical device IFBMs could be used to attach microparticles loaded with a wide variety of therapeutic molecules from antibiotics to prevent post-operative infection to local anesthetics to treat post-operative pain.

描述（由申请人提供）：纵隔炎是心脏直视手术后常见的，有时是毁灭性的并发症。尽管使用了预防性全身性抗生素和改进的手术技术，细菌感染仍然是包括胸骨正中切开术在内的几乎所有外科手术后的严重并发症。当手术部位发生感染时，可能会造成巨大的经济和心理损失，特别是对糖尿病患者、吸烟者、老年人和免疫功能低下的高危患者。防止微生物在手术部位的危险组织中定植的新技术显然可以通过降低感染率而造福社会。对抗生素局部递送的进一步创新是我们开发肽介导系统的动机，该系统可将载药微粒附着在医疗设备上。Affinergy正在开发双功能亲和肽，称为界面生物材料（IFBMs），可促进药物，蛋白质和细胞在医疗器械表面的附着和保留。利用噬菌体展示，我们已经确定了与许多材料和生物制剂具有高亲和力结合的特定肽序列。合成一对这样的多肽作为一个单一的IFBM促进药物、蛋白质或细胞直接附着在医疗设备的表面。虽然我们已经观察到使用抗生素的这项技术有希望的初步数据，但带有载药微粒的肽介导的医疗器械涂层可能具有额外的优势。可能还有其他的药物和其他的医疗设备，我们可能会瞄准这种新的微粒涂层策略。由于存在如此广泛的潜在肽-微粒装置组合，在本提案中，我们将重点开发用于胸骨丝的微粒涂层以预防纵隔炎。因此，本I期研究计划的目标是首先在Affinergy优化载药聚乳酸-羟基乙酸（PLGA）微粒的制备。然后，我们将表征和优化候选PLGA：金属ifbm。最后，我们将研究IFBM靶向微颗粒的抗菌功效和生物相容性，确定微颗粒是否增加了仿能设备涂层技术的潜力。这里提出的目标代表了一个原理验证研究计划，在随后的第二阶段资助期间，该计划将扩大到包括新的抗生素和商业化战略。在未来，微粒子：医疗器械ifbm可以用来附着装载各种治疗分子的微粒子，从用于预防术后感染的抗生素到用于治疗术后疼痛的局部麻醉剂。