Flexible, Conformal, Polymeric Films for Lung Resection Margins

描述（由申请人提供）：多功能生物材料器械备受追捧，因为恢复病变组织的功能通常需要各种设计，有时甚至需要相互冲突的设计（机械、药物释放、生物等）。要求.这对于设计用于预防手术切除后肺肿瘤复发的器械尤其如此。肺癌是美国男性和女性癌症死亡的主要原因，每年有超过160，000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。目前的提案评估了一种灵活的，生物相容的，可生物降解的，低剂量的，缓慢洗脱的紫杉醇负载膜，可以放置在肺癌切除术期间的手术边缘，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，载药薄膜可以防止肿瘤复发后，在体内切除，而不会引起炎症反应或阻碍愈合的手术植入部位。因此，本提案的具体目的是：具体目的1：评价柔性紫杉醇负载聚（碳酸酯-共-酯）膜的药物释放动力学、机械性能和体外抗癌活性。 具体目标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功效。 具体目标3：在大型动物的肺外科手术切缘处确定紫杉醇负载聚（碳酸酯-共-酯）膜的安全性和可行性。 成功完成这些研究的结果将是：1）鉴定能够控制延长的局部药物直接递送到切除部位的膜组合物，其在其功能寿命期间保持柔性和机械完整性; 2）理解该系统在多个细胞周期内将药物递送到肿瘤细胞以提高功效的优点和局限性; 3）识别潜在的设计变化，以改善药物递送、肿瘤致死率、局部组织相容性和伤口愈合，同时保持与当前手术技术和工艺的相容性;和4）为FDA准备未来的试验用器械豁免准备可靠的临床前数据，以预期IRB批准的阶段-I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.