Flexible, Conformal, Polymeric Films for Lung Resection Margins

描述(申请人提供)：多功能生物材料设备备受追捧，因为恢复病变组织的功能通常需要各种设计，有时甚至是相互冲突的设计(机械、药物释放、生物等)。要求。这一点在设计旨在防止肺癌手术切除后复发的装置时尤其正确。肺癌是美国男性和女性癌症死亡的主要原因，每年有超过16万人死亡。即使在完全手术切除的情况下，近40%的早期肺癌患者也会在局部或远处复发。目前的方案评估了一种灵活的、生物相容的、可生物降解的、低剂量、缓慢洗脱的紫杉醇载药膜，它可以在肺癌切除期间放置在手术边缘，在不影响手术部位愈合的情况下防止局部肿瘤复发。重要的是，我们有数据表明，载药膜可以在体内预防肿瘤切除后的复发，而不会引发炎症反应或阻碍手术种植部位的愈合。因此，本建议的具体目标是：特定目的1：评价紫杉醇柔性碳酸酯共聚物薄膜的药物释放动力学、力学性能和体外抗癌活性。特定目的2：确定紫杉醇聚碳酸酯共酯薄膜体内预防肺癌切除后复发的疗效。具体目的3：确定紫杉醇聚碳酸酯共酯薄膜应用于大动物肺外科切除切缘的安全性和可行性。成功完成这些研究的结果将是：1)鉴定一种膜组合物，能够控制局部药物直接输送到切除部位，在其整个功能寿命内保持灵活性和机械完整性；2)了解该系统在多个细胞周期内将药物输送到肿瘤细胞以提高疗效的优势和局限性；3)鉴定潜在的设计变化，以改善药物输送、肿瘤致死性、局部组织相容性和伤口愈合，同时保持与当前外科技术和技术的兼容性；以及4)稳健的临床前数据，用于为FDA准备未来的研究设备豁免，预计将进行IRB批准的I期临床试验，以评估在有限数量的早期I期肺癌患者中的安全性和有效性。

DESCRIPTION (provided by applicant): Multifunctional biomaterial devices are highly sought after since the restoration of function to diseased tissue often requires varied and sometimes conflicting design (mechanical, drug release, biological, etc.) requirements. This is notably true for designing devices intended to prevent lung tumor recurrence following surgical resection. Lung cancer is the leading cause of cancer deaths among men and women in the United States with over 160,000 deaths per year. Even in the setting of complete surgical resection, nearly 40% of patients with early lung cancer will develop recurrent disease at a local or distant site. The current proposal evaluates a flexible, biocompatible, biodegradable, low dose, slow eluting paclitaxel-loaded film that can be placed at the surgical margin during lung cancer resection to prevent local tumor recurrence without impairing healing of the surgical site. Importantly, we have data demonstrating that drug-loaded films can prevent tumor recurrence following resection in vivo without invoking an inflammatory response or impeding healing at the surgical implantation site. Accordingly, the specific aims of this proposal are: SPECIFIC AIM 1: Evaluate the drug release kinetics, mechanical properties, and in vitro anti-cancer activity of flexible paclitaxel-loaded poly(carbonate-co-ester) films. SPECIFIC AIM 2: Determine the efficacy of paclitaxel-loaded poly(carbonate-co-ester) films to prevent recurrence of lung tumors following resection in vivo. SPECIFIC AIM 3: Determine the safety and feasibility of paclitaxel-loaded poly(carbonate-co-ester) films applied at the pulmonary surgical resection margin in a large animal. The results from successful completion of these studies will be: 1) identification of a film composition capable of controlled prolonged local drug delivery directly to the site of resection that maintains flexibility and mechanical integrity throughout its functional life time; 2) understanding of the advantages and limitations of this system to deliver drugs to tumor cells over multiple cell cycles to increase efficacy; 3) identification of potential design variations to improve drug delivery, tumor lethality, local tissue compatibility, and wound healing while remaining compatible with current surgical techniques and technology; and 4) robust pre-clinical data for the preparation of a future Investigational Device Exemption for the FDA in anticipation of an IRB- approved Phase-I clinical trial to assess safety and efficacy in a limited number of patients with early stage I lung cancer.