Field-Induced Magnetic Nanoparticle Drug Delivery BME 273 Group 15 Team Leader : Ashwath Jayagopal (BME, EE, MATH) Members : Sanjay Athavale (BME) and Amit Parikh (BME) Advisor : Dr. Dennis Hallahan, Chairman of Radiation Oncology and Professor of Biomedical Engineering and Radiation Oncology, Vanderbilt University Dr. Paul King, PE, Associate Professor of Biomedical Engineering, Mechanical Engineering and Anesthesiology, Vanderbilt University

Project Objectives Develop an effective method for site-specific drug delivery to a tumor using the properties of magnetic nanoparticles Design a device that provides the optimum magnetic field effect needed for delivery of drug-containing particles to an exact location Use the device in conjunction with irradiation and biological treatment processes to enhance delivery Reduce problems associated with current treatment methods dramatically

Overview of Magnetic Technology Using recently developed methods, medications can be encased to magnetic nanoparticles Given antibody coating, avoids immune reaction, yet lasts in circulation Superparamagnetic iron oxide nanoparticles exhibit strong magnetic properties given an externally applied field Can be produced in uniform sizes and properties (Georgia Tech consortium) Guided missiles that can deliver to affected area without harming healthy tissue – enhanced by irradiation of tumor area

Rationale and Market Appeal Could potentially be used for treatment of cancer and non-cancer illness Since million diagnosed with cancer, 5-year survival rate is 62% Current side effects associated with treatment : lower blood counts, flu-like symptoms, hair loss, swelling, scars and wounds, weight fluctuation, nausea, diarrhea, healthy cell death Magnetic nanoparticle treatment : site-specific administration, duration of dosage controlled, reduced side effects, more effective treatment R&D costs <$2 million, clinical trials <$1 million, procedure <<$4,000, US drug delivery market estimated worth : $24 billion (sources : American Cancer Society 2003, Lynne Falk and Chris Iversen BME 273 Design Webpage, Scripps Reports 2001)

Our solution Design an electromagnet matrix that precisely controls nanoparticle drug delivery of doxorubicin (Upjohn, 1987) to a tumor bearing mouse Irradiate tumor area Possibly use biological factors in our design (TNF, EGF, albumin coat) To quantify performance, use fluorescent tracers to indicate concentration, location, and dosage duration, as well as magnetometer Michigan State Univ. 2003, s/ffmed/

Obstacles Nanoparticle aggregation Tumor permeability Drug delivery location and duration Imaging of procedure is challenging Type of Electromagnet, controlling magnetic field Univ. Central Florida 2003 : unix.oit.umass.edu/~nano/NewFiles/Over34_UCFlorida.pdf

Current Achievements Have decided on 4 potential designs Collaborated with multiple VUMC personnel and received useful feedback on our design – potential sources of error in design reduced Secured facilities, resources (nanoparticles, mice), and funding Have established contacts with the Georgia Institute of Technology magnetic carrier consortium, and Chemicell Gmbh, as well as Duramag and Bunting Magnetics (electromagnet retailers) Have recorded observations on nanoparticles and their properties

Future Objectives Conduct experiments on mice tumors using nanoparticles Continue consultation with contacts to incorporate the most effective electromagnet – nanoparticle combination in our design Purchase electromagnet, construct a magnetometer, begin constructing prototypes Continue research on patents, develop revised IWB and begin designsafe immediately, obtain feedback on current progress from advisors (King, Hallahan)