Abstract
Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity. Here, we describe the development of a chemotherapy-loaded polymer buttress, to be implanted along the surgical margin at the time of tumor resection, for achieving local and prolonged release of a new anticancer agent, eupenifeldin. We prepared five different formulations of buttresses with varying amounts of eupenifeldin, and additional external empty polymer coating layers (or thicknesses) to modulate drug release. The in vitro eupenifeldin release profile depends on the number of external coating layers with the formulation of the greatest thickness demonstrating a prolonged release approaching 90 days. Similarly, the long-term cytotoxicity of eupenifeldin-loaded buttress formulations against murine Lewis lung carcinoma (LLC) and human lung carcinoma (A549) cell lines mirrors the eupenifeldin release profiles and shows a prolonged cytotoxic effect. Eupenifeldin-loaded buttresses significantly decrease local tumor recurrence in vivo and increase disease-free survival in a lung cancer resection model.