Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations

Neuroblastoma is the most common extra-cranial childhood tumor and current treatment requires surgical resection and multi-drug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study we have aimed to develop a controlled release implant system to deliver cisplatin in tumor/tumor resection area. Silk fibroin, a biodegradable, non-immunogenic biopolymer was employed to encapsulate different doses of cisplatin in a reservoir system. The physical integrity of the reservoirs was characterized by evaluating the crystalline structure of silk secondary structure using Fourier Transform Infrared (FTIR) spectroscopy. The in vitro release of cisplatin was evaluated in phosphate buffered saline at 37°C and the reservoirs were able to release the drug up to 30 days. The cytotoxicity of cisplatin and cisplatin reservoirs were tested on KELLY cells. Cytotoxicity data showed 3.2 µg/mL cisplatin was required to kill 50 percent of the cell population and the released cisplatin from the silk reservoirs showed significant cytotoxicity up to 21 days. Intra- tumoral implantation of silk reservoirs into an orthotopic neuroblastoma mouse model decreased tumor growth significantly when compared to controls. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site.