ARRAY: A novel polymeric mesh for prophylactic antibiotic protection of cardiac implantable electronic devices

ARRAY：一种新型聚合物网，用于心脏植入电子设备的预防性抗生素保护

• 批准号: 10600803
• 负责人: Jiayi Yu
• 金额: $ 100万
• 依托单位: 21MEDTECH LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10600803
• 关键词: Address; Amino Acids; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Bacteria; Cardiovascular system; Cefazolin; Colony-forming units; Cyclic GMP; Data; Development; Device Removal; Devices; Dose; Drug Kinetics; Electronics; Esters; Exhibits; Film; Financial Hardship; Formulation; Goals; Gram-Negative Bacteria; Hernia; Hospital Costs; Hospitalization; Hour; Implant; In Vitro; Incidence; Infection; Infection prevention; Inflammatory Response; Kinetics; Label; Licensing; Marketing; Methods; Minocycline; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Polyesters; Polymers; Population; Postoperative Period; Preparation; Procedures; Quality of life; Rattus; Residual state; Rifampin; Risk; Safety; Series; Skin; Sterilization; Surgical Replantation; Thick; Time; Titanium; Urea; aging population; biodegradable polymer; biomaterial compatibility; cardiac implant; clinically relevant; combat; commercialization; comorbidity; comparative; controlled release; copolymer; design; dosage; drug release profile; implant associated infection; implantable device; implantation; improved; in vivo; infection burden; infection management; infection rate; innovation; microbial; mortality; non-opioid analgesic; novel; pathogen; prevent; prophylactic; risk selection; safety assessment; soft tissue; standard of care; stoichiometry; success; surgery outcome; tissue repair

PROJECT SUMMARY 21MedTech, LLC is developing the ARRAYTM antibiotic-loaded envelope to address the need for novel methods to tackle rising rates of infections associated with cardiovascular implantable electronic devices (CIEDs). There were 1.5 million CIEDs implanted in 2011 and that number continues to grow. Between 1% and 4% of implantations result in infection, which have potential for severe morbidity and mortality outcomes. The mortality rate from CIED associated pocket infections can be as high as 66% if the device is not removed and up to 18% with device removal and antibiotic therapy. To address the need for additional methods to reduce or prevent these infections, 21MedTech is developing the ARRAY envelope for longer-term protection. The ARRAY envelope employs a novel bioresorbable polymer film that facilitates the controlled release of rifampin and minocycline locally following surgical implantation of a CIED. The envelope is highly tunable, enabling control over drug release and degradation time, and has been shown to be highly biocompatible in vivo. Prior to this Direct to Phase II proposal, 21MedTech has demonstrated safety and efficacy of the envelope material in vitro and in vivo and has demonstrated feasibility with controlled release of rifampin and minocycline over 28 days. 21MedTech has also shown improved drug release profiles over the commercially available TYRXTM envelope in vitro, which exhibits a burst release (>90%) in the first 24 hours. The goals of this proposal will be to optimize release of antibiotics from the envelope, assess safety and efficacy, and to determine the effective dose in a well-defined animal model. Success with these goals will advance the ARRAY envelope towards FDA clearance. Commercialization of the ARRAY envelope will improve CIED surgical outcomes and improve patient quality of life by reducing CIED associated infections.

项目总结 21 MedTech，LLC正在开发ARRAYTM抗生素信封，以满足对新方法的需求 以应对与心血管植入式电子设备(CIED)相关的不断上升的感染率。那里 2011年植入了150万个CIED，而且这个数字还在继续增长。在1%至4%之间 植入会导致感染，这可能会导致严重的发病率和死亡率。死亡 如果不取出装置，CIED相关口袋感染的发生率可能高达66%，高达18% 通过移除设备和抗生素治疗。解决减少或预防的其他方法的需求 针对这些感染，21MedTech正在开发用于长期保护的阵列包膜。该阵列 信封采用了一种新型的可生物吸收的聚合物薄膜，有助于利福平和利福平的控制释放 手术植入CIED后局部应用米诺环素。包络高度可调，支持控制 超过药物释放和降解时间，并已被证明在体内具有高度的生物相容性。在此之前 关于第二阶段的提案，21MedTech已经在体外证明了包膜材料的安全性和有效性 和体内，并已证明了利福平和米诺环素在28天内控释的可行性。 21 MedTech还显示，与商用TYRXTM信封相比，药物释放情况有所改善 在体外，在最初的24小时内表现出爆发式释放(&gt；90%)。这项提案的目标将是优化 从包膜中释放抗生素，评估安全性和有效性，并确定有效剂量 定义明确的动物模型。这些目标的成功将推动阵列包络获得FDA的批准。 阵列包膜的商业化将改善CIED手术结果并提高患者质量 通过减少与CIED相关的感染来延长生命。