Flexible, Conformal, Polymeric Films for Lung Resection Margins

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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.