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

项目摘要 21MedTech，LLC正在开发ARRAYTM药物装载信封，以满足对新方法的需求 以解决与心血管植入式电子设备（CIED）相关的感染率上升问题。那里 2011年植入了150万个CIED，而且这个数字还在继续增长。1%至4%之间 复发导致感染，这有可能导致严重的发病率和死亡率。死亡 如果不取出器械，CIED相关囊袋感染的发生率可高达66%， 取出装置并进行抗生素治疗为了满足对减少或预防的额外方法的需求， 为了应对这些感染，21 MedTech正在开发ARRAY信封以提供长期保护。阵列 包膜采用了一种新型的生物可吸收聚合物膜， 在CIED的手术植入后局部施用米诺环素。包络是高度可调的，使控制 在药物释放和降解时间内，并且已经显示出在体内具有高度生物相容性。在此之前 针对II期提案，21MedTech已在体外证明了包膜材料的安全性和有效性 并且已经证明了在28天内控制释放利福平和米诺环素的可行性。 21MedTech还显示出比市售TYRX ™包膜更好的药物释放特性 在体外，其在前24小时内表现出突释（>90%）。该提案的目标是优化 从信封中释放抗生素，评估安全性和有效性，并确定有效剂量， 明确的动物模型。这些目标的成功将推动ARRAY信封获得FDA批准。 ARRAY信封的商业化将改善CIED手术结果并提高患者质量 减少CIED相关感染。

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.