Zoom Meeting (Information posted at the end of the announcement)
Chemotherapy-Eluting Intraperitoneal Implants for Advanced Stage Ovarian Cancer Treatment
The objective of this work was to develop an implant for sustained chemotherapy delivery directly into the abdomen, also known as intraperitoneal (IP) chemotherapy. IP chemotherapy is used to treat peritoneal metastasis resulting from several advanced gynecologic and gastrointestinal cancers and has shown promise for improving survival in ovarian cancer (OC). Its adoption, however, has suffered greatly due to the need for significant resources to administer effectively and undesirable toxicities and side effects that result from the high doses of drug delivered. We have previously showed that an implantable IP device that delivers sustained doses of chemotherapy over time can be equally effective in treating OC in mice and less toxic than intermittent high-dose IP drug injections.
To translate that work to a clinically relevant implantable delivery system, a biocompatible composite implant material was developed from medical-grade materials containing microparticulate cisplatin, a commonly used drug in OC treatment. The material was designed to match mechanical properties of abdominal organs for placement in the peritoneal cavity without inducing material-related toxicity. Sheets fabricated from the cisplatin-loaded composite material were evaluated in vitro for sustained drug release and for bioactivity against multiple OC cell lines. Three-dimensional implant geometries were designed and prototyped from the sheets to facilitate implant deployment using standard laparoscopic surgical ports.
The impact of sustained chemotherapy delivery achieved by the IP implant is anticipated to be greatest against microscopic tumor nodules that are left behind following debulking surgery, which precedes chemotherapy treatment in OC patients. Most animal models of OC have failed to replicate this disperse minimal disease and, therefore, do not reflect the expected clinical treatment response. In order to address this shortcoming, a new OC mouse model with wide abdominal spread of microscopic tumors was developed and characterized in this work to provide a clinically translatable model to study the efficacy of the IP implant, as well as other novel treatments for OC.
The implications for an implant that can make IP chemotherapy more effective and accessible are greater in resource-limited settings. Design reviews and surveys of practicing physicians in India have revealed the eagerness for new technology adoption and the potential for an IP implant to supplement and integrate into existing peritoneal metastasis treatment regimens. The present work carries implications for treating patients worldwide with advanced OC by improving both patient compliance and physician adoption of IP chemotherapy. The technology developed in this work ultimately serves as a platform for sustained local chemotherapy delivery to the abdomen and will help guide future treatment efforts in peritoneal metastasis management.
Thesis Supervisor:
Michael J. Cima, PhD
David H. Koch Professor of Engineering, MIT
Thesis Committee Chair:
Darrell J. Irvine, PhD
Professor of Materials Science & Engineering and Biological Engineering, MIT
Thesis Readers:
Marcela G. del Carmen, MD, MPH
Professor of Obstetrics, Gynecology and Reproductive Biology, HMS
Robert S. Langer, ScD
David H. Koch Institute Professor, MIT
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Zoom invitation -
Kriti S. Subramanyam is inviting you to a scheduled Zoom meeting.
Topic: Kriti S. Subramanyam Thesis Defense
Time: Thursday, June 3, 2021 10:30 AM Eastern Time (US and Canada)
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