The most effective treatment for patients with localized, early-stage non-small cell lung cancer (NSCLC) is surgical resection.  The current standard is to remove a significant amount of lung tissue (lobectomy), however, this can further compromise already limited pulmonary reserve in many patients. Lung-sparing surgeries (i.e. wedge resection) have been developed for this reason, but they are associated with a 2- to 3-fold increase in local recurrence due to microscopic residual tumor cells at the resection margin. Once local recurrence occurs, the outcomes are dismal, with a median survival of 40 months, as many patients are not candidates for further surgery and chemotherapy and radiotherapy are largely palliatives in this setting. Therefore, there is a significant need for adjuvant treatment options to prevent local recurrence after lung-sparing surgery.  We have designed, synthesized, and evaluated high-dose paclitaxel- loaded polymeric films which can be implanted at the time of surgery.<br/>Films composed of either: 1) poly(1,2-glycerol carbonate)-graft-succinic acid-paclitaxel (PGC–PTX), which enables high, controlled PTX loadings of up to 74 wt%; or 2) PGC-PTX + physically entrapped PTX (PTX-(PGC-PTX)), which enables PTX loadings up to 120 %wt were evaluated. The PGC polymer backbone is composed of biocompatible building blocks—glycerol and carbon dioxide. PGC-PTX drug-loaded films demonstrate prolonged release of four to over seven weeks depending upon drug loading, without initial burst release behavior. In contrast, PGC-PTX-PTX releases PTX faster as the physically entrapped PTX is first released followed by the PTX conjugated to the PGC. Preliminary <i>in vivo</i> studies show decreased local recurrence with PTX loaded films compared to untreated controls and systemic PTX, and additional studies are on-going. These results emphasize the importance of supplementing wedge resection surgery with local drug delivery strategies to improve the prognosis for lung cancer patients.<br/>

Novel biodegradable drug-loaded films for the prevention of lung tumor recurrence

256th National Meeting (2018)

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