Flexible, Conformal, Polymeric Films for Lung Resection Margins

描述（由申请人提供）：多功能生物材料设备受到高度追捧，因为病变组织的功能恢复通常需要各种不同的，有时是相互冲突的设计（机械，药物释放，生物学等）要求。这对于设计旨在预防手术切除后肺肿瘤复发的设备尤其正确。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%的早期肺癌患者会在局部或远处复发。目前的建议评估了一种灵活的、生物相容性的、可生物降解的、低剂量的、缓慢洗脱的紫杉醇负载膜，这种膜可以在肺癌切除的手术边缘放置，以防止局部肿瘤复发而不损害手术部位的愈合。重要的是，我们有数据表明，载药薄膜可以在体内防止肿瘤切除后复发，而不会引起炎症反应或阻碍手术植入部位的愈合。因此，本提案的具体目的是：具体目的1：评估柔性紫杉醇负载聚（碳酸酯-共酯）薄膜的药物释放动力学、机械性能和体外抗癌活性。特异性目的2：确定紫杉醇负载的聚（碳酸酯-共酯）膜在体内预防肺肿瘤切除术后复发的疗效。特定目的3：确定在大型动物肺外科切除边缘应用紫杉醇负载聚（碳酸酯-共酯）薄膜的安全性和可行性。成功完成这些研究的结果将是：1)鉴定出一种膜组合物，这种膜组合物能够控制长期的局部药物直接递送到切除部位，并在其功能寿命期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点和局限性；3)确定潜在的设计变化，以改善药物传递、肿瘤致死性、局部组织相容性和伤口愈合，同时保持与当前手术技术和技术的兼容性；4)稳健的临床前数据，为未来FDA的研究器械豁免做准备，以期待IRB批准的I期临床试验，以评估有限数量的早期I期肺癌患者的安全性和有效性。

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.