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

基本信息

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
项目类别：
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

项目摘要

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、有时甚至是毁灭性的并发症。尽管使用预防性全身抗生素和改进的手术技术，细菌感染仍然是包括正中胸骨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，可能会造成毁灭性的后果，造成巨大的经济和心理损失，尤其是对于糖尿病患者、吸烟者、老年人和免疫功能低下等高危患者。防止手术部位高危组织微生物定植的新技术可以通过降低感染率来明显造福社会。抗生素局部递送需要进一步创新，这是我们开发肽介导系统以将载药微粒附着到医疗设备上的动机。 Affinergy 正在开发双功能亲和肽，称为界面生物材料 (IFBM)，可促进药物、蛋白质和细胞在医疗设备表面的附着和保留。通过噬菌体展示，我们已经鉴定出与许多材料和生物制品具有高亲和力结合的特定肽序列。将一对这样的肽合成为单个 IFBM 可促进药物、蛋白质或细胞直接附着到医疗设备的表面。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，但用载药微粒对医疗器械进行肽介导的涂层可能具有额外的优势。我们可能会用这种新颖的微粒涂层策略来瞄准其他药物和其他医疗设备。由于存在如此广泛的潜在肽-微粒装置组合，因此在本提案中，我们将重点开发用于胸骨线的微粒涂层，以预防纵隔炎。因此，该一期研究计划的目标是首先优化 Affinergy 的载药聚乳酸-乙醇酸 (PLGA) 微粒制剂。然后，我们将表征和优化候选 PLGA：金属 IFBM。最后，我们将检查 IFBM 靶向微粒的抗菌功效和生物相容性，确定微粒是否会增加 Affinergy 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，该计划将在随后的第二阶段资助期间扩大到包括新的抗生素和商业化策略。未来，微粒：医疗设备IFBM可用于附着载有多种治疗分子的微粒，从预防术后感染的抗生素到治疗术后疼痛的局部麻醉剂。公共卫生相关性：术后感染是心脏直视手术后常见的、有时甚至是毁灭性的并发症。尽管使用预防性全身抗生素并改进手术技术，感染仍然是一个严重的并发症。局部抗生素递送方面进一步创新的需要是我们开发肽介导的附着系统的动力，用于将载药微粒附着到医疗设备上。 Affinergy 正在开发双功能亲和肽，称为界面生物材料 (IFBM)，可促进药物、蛋白质和细胞在医疗设备表面的附着和保留。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，但用载药微粒对医疗器械进行肽介导的涂层可能具有额外的优势。我们可能会利用这种新颖的微粒涂层策略来瞄准其他药物和其他医疗设备。在这项提案中，我们重点开发用于胸骨导丝的微粒涂层，以便在心脏直视手术后局部输送抗生素。未来，微粒：医疗设备IFBM可用于附着载有多种治疗分子的微粒，从预防术后感染的抗生素到治疗术后疼痛的局部麻醉剂。