BME PhD Prospectus Defense - Carl Beigie

1:00 pm on Tuesday, January 21, 2014
44 Cummington Mall, Room 203
Prof. Joyce Wong, Biomedical Engineering (Advisor, Chair)
Prof. Arthur F. Stucchi, School of Medicine
Prof. Shyamsunder Erramilli, Physics & Biomedical Engineering
Prof. Allison Dennis, Biomedical Engineering

Title: "A Theranostic Approach to the Prevention and Imaging of Intraperitoneal Adhesions using Drug Loaded Hybrid Liposome-Iron Oxide Nanoparticles"

It is estimated that nearly 100% of patients develop some type of intraperitoneal adhesion, or fibrous band formation between tissues, following invasive intra-abdominal and pelvic surgery. At least one third of these are readmitted an average of two times over a subsequent two-year period due to complications such as chronic abdominal or pelvic pain, infertility in women, and intestinal obstruction. Overall, adhesion-related diseases are estimated to cost the American health care system $5 billion annually. The goal of this project is to develop a theranostic tool for the prevention and non-invasive imaging of potential intraperitoneal adhesions. Specifically, a hybrid drug-containing liposomal formulation of encapsulated iron oxide nanoparticles will be developed for targeting adhesion sites and for delivery of proven adhesion reducing therapeutics. A library of liposomal formulations of different charges and sizes will be screened using IVISŪ for bio-distribution in a rat model for peritoneal dispersion and retention. The targeting ligands, Intracellular adhesion molecule-1 (ICAM-1) and fibrin, will be assessed for specificity to adhesion formation sites using Quartz Crystal Microbalance (QCM) and an in vivo model of adhesion. Release of a Neurokinin-1 receptor antagonist will be tailored to maintain therapeutic levels for 72 hours in the peritoneum. Iron oxide nanoparticles will be co-encapsulated with therapeutic in optimized liposomal carriers targeted towards adhesion formation sites and visualized using Magnetic Resonance Imaging (MRI). The end result of this work will be a solution, which a clinician can easily administer to the peritoneum prior to wound closure. The easily dispersible liposomes in conjunction with the targeting moiety will accumulate at specific adhesion sites without required “guess work” of the surgeon. Finally, the MRI capability will allow for a non-invasive “second look” and subsequently offer a pathway for diagnosis and improved clinical outcome.