STTR Phase I: Cardiotropic Atorvastatin Liposomes for Myocardial Reperfusion Injury

这个小企业技术转让（STTR）第一阶段项目的更广泛影响/商业潜力涉及患有冠状动脉疾病并接受血管成形术或搭桥手术等手术的大量人群对药物治疗的迫切需求。虽然这些干预措施在纠正流向心脏组织的血流减少方面是有效的，但也会导致组织损伤，被归类为缺血再灌注损伤（IRI）。这种残余损伤是再住院、延长住院时间、心力衰竭和死亡的主要原因，因此迫切需要药物治疗来解决这种残余损伤。通过部署用于药物递送的心脏靶向载体的拟议技术，将有可能实现有效的心脏保护，这将减少患者的痛苦和对接受再灌注手术的患者的医疗保健系统的经济负担。这项颠覆性技术将影响价值16亿美元的心肌再灌注损伤市场，并影响美国每年接受血管成形术或搭桥手术治疗的100多万冠状动脉疾病患者的护理标准。这项小企业技术转让（STTR）I期项目将开发阿托伐他汀脂质体（CATLIP），以提供阿托伐他汀对心脏的心脏保护作用，安全和有效。创新的CATLIP技术将提供治疗量的阿托伐他汀到心脏组织治疗IRI。目前的给药方法不足以达到临床疗效所需的药物浓度。服务于开发心肌靶向治疗以减轻IRI的长期目标，该原理验证项目的研究目标是实现阿托伐他汀在心脏组织中的有效递送。CATLIP的靶向方法是基于一种小分子靶向载体，该载体选择性地结合暴露在受损心脏组织中的心肌球蛋白。研究小组将制备和表征负载阿托伐他汀的脂质体，并在表面修饰有心肌靶向载体。将在心肌梗死动物模型中测试该制剂，以确定心脏组织中的阿托伐他汀递送。该项目的成功实施将创造一种用于治疗心脏IRI的专利产品，并展示靶向技术与其他药物一起应用于相同医疗条件的潜力。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project pertains to the critical need for pharmacologic treatments in large populations that suffer from coronary artery disease and that are subjected to procedures such as angioplasty or bypass surgery. While effective in correcting the reduced flow of blood to the heart tissue, these interventions also cause tissue damage categorized as ischemia reperfusion injury (IRI). A pharmacologic treatment is critically needed to address this residual injury that is a major cause of rehospitalization, prolonged hospital-stay, heart failure, and mortality. By deploying the proposed technology of heart-targeted vehicle for drug delivery, it will be possible to achieve effective cardioprotection, which will reduce patient distress and economic burden on the healthcare system for patients undergoing reperfusion procedures. This disruptive technology will impact myocardial reperfusion injury market worth $1.6 billion and influence the standard of care for over 1 million coronary artery disease patients that are treated by angioplasty or bypass surgery each year in the United States.This Small Business Technology Transfer (STTR) Phase I project will develop Cardiotropic Atorvastatin Liposomes (CATLIP) to deliver cardioprotective benefits of atorvastatin to the heart, safely and effectively. The innovative CATLIP technology will deliver therapeutic amounts of atorvastatin to the heart tissue for treatment of IRI. Current methods of administration are inadequate in reaching the drug concentration needed for clinical efficacy. Serving a long-term goal of developing a myocardia-targeted treatment to mitigate IRI, the research objective of this proof-of-principle project is to attain effective delivery of atorvastatin in the heart tissue. CATLIP’s targeting approach is based on a small molecule targeting vector that selectively binds to the cardiomyosin exposed in the injured heart tissue. The research team will prepare and characterize liposomes loaded with atorvastatin and modified on the surface with the cardiotropic targeting vector. This preparation will be tested in an animal model of myocardial infraction to determine atorvastatin delivery in the heart tissue. Successful implementation of this project will create a proprietary product for treatment of IRI of the heart and demonstrate the potential of a targeting technology for application with other drugs for the same medical condition.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.