Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations
Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study, we have aimed...
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| Published in | Journal of pharmaceutical sciences Vol. 108; no. 8; pp. 2748 - 2755 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.08.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-3549 1520-6017 1520-6017 |
| DOI | 10.1016/j.xphs.2019.03.019 |
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| Abstract | Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug 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 or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used 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 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% 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 with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site. |
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| AbstractList | 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. Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug 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 or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used 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 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% 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 with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site.Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug 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 or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used 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 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% 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 with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site. Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug 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 or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used 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 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% 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 with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site. |
| Author | Zeki, Jasmine Yavuz, Burcin Taylor, Jordan Coburn, Jeannine M. Kaplan, David L. Harrington, Kristin Chiu, Bill Ikegaki, Naohiko |
| AuthorAffiliation | 2 Department of Surgery, Stanford University, Stanford, CA, USA 3 Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA 1 Department of Biomedical Engineering, Tufts University, Medford, MA, USA 4 Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA |
| AuthorAffiliation_xml | – name: 2 Department of Surgery, Stanford University, Stanford, CA, USA – name: 4 Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA – name: 1 Department of Biomedical Engineering, Tufts University, Medford, MA, USA – name: 3 Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA |
| Author_xml | – sequence: 1 givenname: Burcin surname: Yavuz fullname: Yavuz, Burcin organization: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155 – sequence: 2 givenname: Jasmine surname: Zeki fullname: Zeki, Jasmine organization: Department of Surgery, Stanford University, Stanford, California 94305 – sequence: 3 givenname: Jordan surname: Taylor fullname: Taylor, Jordan organization: Department of Surgery, Stanford University, Stanford, California 94305 – sequence: 4 givenname: Kristin surname: Harrington fullname: Harrington, Kristin organization: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155 – sequence: 5 givenname: Jeannine M. surname: Coburn fullname: Coburn, Jeannine M. organization: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155 – sequence: 6 givenname: Naohiko surname: Ikegaki fullname: Ikegaki, Naohiko organization: Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois 60612 – sequence: 7 givenname: David L. surname: Kaplan fullname: Kaplan, David L. email: david.kaplan@tufts.edu organization: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155 – sequence: 8 givenname: Bill surname: Chiu fullname: Chiu, Bill email: bhsc@stanford.edu organization: Department of Surgery, Stanford University, Stanford, California 94305 |
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| Copyright | 2019 American Pharmacists Association Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. |
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| Keywords | site-specific delivery controlled release drug delivery system biomaterials solid dosage forms cancer chemotherapy |
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| Title | Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations |
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