Cisplatin-Eluting Pellets for Malignant Pleural Effusion---in vivo and Animal Cancer Models

Malignant pleural effusion(MPE) is a common and debilitating complication associated with numerous types of advanced oncologic diseases. The prognosis of patients with MPE is poor, with the average survival time after diagnosis being 3 to 6 months. Traditionally, the treatment of MPE is generally purely palliative. Chemical or physical pleural abrasion, pleurodesis with sclerosing agents or talc are palliative treatments usually administered with concomitant systemic chemotherapy. Their objective is to alleviate the dyspnea but not to sterilize the pleural tumor. Recently, some investigators hypothesized that injecting agents with the potential to kill the malignancy into the pleural cavity( i.e. intrapleural chemotherapy) might be effective and even curative . The rationale for the use of cytotoxic agents as intracavitary administration is the intense and extended exposure to local tissues with reduced systemic effects . So far, several drugs have been used intrapleurally such as platinum compounds , etoposide , paclitaxel and pemetrexed . However, results were suboptimal and not superior to palliative-intent therapy. The overall response rate(complete plus partial) of MPE after intrapleural chemotherapy was less than 50%. The major mechanism of failure for intrapleural chemotherapy is the short half life and rapid drug absorption in the contaminated serous tissue. In animal model, intrapleural drug concentration dropped below therapeutic level within 48 hours. Hence, a delivery system loaded with chemotherapeutic agent at tumor site( i.e. localized chemotherapy) which provide a high and sustained local concentration of the drug detrimental to malignant cells might shown lots of potential. However, most reported chemotherapeutic drug delivery systems had important limitations; either with "short" releasing period /hard to manipulate or might lead to unwanted local wound complications(ex: delayed healing, infection). The purpose of this study is to develop novel cisplatin-eluting pellets to insert intrapleurally and to provide sustained-release delivery of cisplatin. In our 2 -year proposal, two phases of study will be performed: Part 1 : Pellets fabrication and in vitro evaluation Part 2: In vivo evaluation 2-1 Establish of mice MPE model 2-2 In vivo healthy mice model for safety evaluation. 2-3 In vivo MPE mice model for therapeutic effect evaluation

Project ID:PC10408-2660
External Project ID:MOST104-2314-B182-048