Pleural Mesothelioma (PM) is a rare tumor arising from mesothelial cells. The prognosis is poor due to the frequent peritoneal metastases. Cisplatin (cisPt) is the first-line therapy but is often discontinued due to dose-limiting toxicity. We have developed a cisPt-loaded hyaluronan (NaHA) film for loco-regional chemotherapy of PM. The film is designed to be stuck on the pleura surface after surgical resection of primary tumor . cisPt is released from the film in a prolonged manner thus maintaining high local concentrations overtime. Its efficacy in reducing metastases was proven in a rat model. In a second in vivo study, despite the high drug concentrations reached, no signs of cisPt-related toxicity were detected compared to the intravenous cisPt solution. This great result was due to cisPt complexation with NaHA, demonstrated by various analytical techniques. Upon film dissolution, cisPt and NaHA existed as nanoparticles of cisPt/NaHA macromolecular complex.
Learning Objectives:
To learn the film technology as drug delivery system.
To understand efficacy and safety of cisplatin/hyaluronan complex.
To appreciate the potential of treating cancer locoregionally to prevent relapses.
To show the cytotoxicity of cisplatin/hyaluronan complex in cancerous cell lines other than pleural mesothelioma.