Zoom Meeting (Information posted at the end of the announcement)
Single Subcompartment Drug Delivery
Most drugs are administered systemically, intravenously or orally, but there are inherent challenges with these methods. Drug distributes throughout the body, which results in two main challenges: (1) poor efficacy due to the under accumulation of drug at sites of disease and (2) side effects due to the over accumulation of drug in healthy tissue where the drug may interact with off-target molecules or cells. Several strategies have been developed to improve drug distribution. Nanoparticles and antibody-drug conjugates use targeting molecules to increase drug accumulation at certain sites or cells, leading to improved outcomes, but only a handful of such therapies have had a clinical impact thus far. Further advancements have also been made to change the administration route of drugs rather than relying on molecular targeting. The body can be broken down into a series of compartments that encompass different cavities or organ systems, such as the peritoneum, urinary tract, or eye. Drugs can be directly delivered to a single compartment through an infusion system or drug-eluting implant. Single compartment drug delivery increases drug concentration at the target site and minimizes drug exposure at distant sites of the body, leading to improved outcomes and reduced side effects. Several such strategies have successfully been commercialized.
Improved understanding of physiology and disease progression at the cellular and molecular level has led to further defining of disease pathology beyond the single compartment. The brain, for example, has been divided into several microstructures, each of which has a different function that can be disrupted leading to disease. Tumors have also been further defined as separate entities from healthy organs due to genetic, immune, and microenvironment variations. We hypothesize that targeting single subcompartments can further advance single compartment drug delivery strategies.
We present novel examples of single subcompartment drug delivery devices for treating and diagnosing disease. Chronic brain implants were developed to elicit minimal scarring and deliver microliters of drug to distinct microstructures suspect in disease, such as a seizure focus. An implant and computational platform was further developed to deliver drug microdoses to tumor, analyze the tumor response to each drug, and computationally predict potential efficacy of each drug. This platform successfully predicted systemic treatment outcomes in ovarian patient-derived xenograft tumors with greater than 90% accuracy, with the potential for clinical implementation in the near-term. The results of both studies represent the promise of single subcompartment drug delivery to improve outcomes for patients.
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:
Robert S. Langer, ScD
David H. Koch Institute Professor, MIT
S. John Weroha, MD, PhD
Associate Professor of Oncology
Mayo Clinic College of Medicine and Science
------------------------------------------------------------------------------------------------------
Zoom invitation -
Max J. Cotler is inviting you to a scheduled Zoom meeting.
Topic: Max J. Cotler Thesis Defense
Time: April 21, 2021 10:00 AM Eastern Time (US and Canada)
Your participation is important to us: please notify hst [at] mit.edu, at least 3 business days in advance, if you require accommodations in order to access this event.
Join Zoom Meeting
https://mit.zoom.us/j/97320120239?pwd=ZlJreDNYOFZuN3Z2RkF4c2wyd1E2Zz09
Password: 562867
One tap mobile
+16699006833,,97320120239# US (San Jose) 16465588656,,97320120239# US
+(New York)
Meeting ID: 973 2012 0239
US : +1 646 558 8656 or +1 669 900 6833
International Numbers: https://mit.zoom.us/u/ax5JcrmPC
Join by SIP
97320120239 [at] zoomcrc.com (97320120239[at]zoomcrc[dot]com)
Join by Skype for Business