Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations
| Autor: | Jasmine Zeki, Naohiko Ikegaki, Burcin Yavuz, Bill Chiu, Jordan S. Taylor, David L. Kaplan, Jeannine M. Coburn, Kristin Harrington |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Population
Cell Mice Nude Pharmaceutical Science Fibroin Antineoplastic Agents 02 engineering and technology 030226 pharmacology & pharmacy Article Mice Neuroblastoma 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans education Cytotoxicity Cisplatin education.field_of_study Chemistry Bombyx 021001 nanoscience & nanotechnology medicine.disease Controlled release Disease Models Animal medicine.anatomical_structure Delayed-Action Preparations Cancer research Female Fibroins 0210 nano-technology medicine.drug |
| Zdroj: | J Pharm Sci |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2019.03.019 |
| Popis: | 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. Intratumoral 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|