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, Dr. John Zhang, lead investigator) Guided missiles that can deliver to affected area without harming healthy tissue – enhanced by irradiation of tumor area

Rationale and Market Appeal 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 Could potentially benefit all cancer patients (sources : American Cancer Society 2003, Lynne Falk and Chris Iversen BME 273 Design Webpage, Scrips 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 and use biological factors to aid in nanoparticle delivery (TNF, antibody albumin coating) 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 challenging Limits of Facilities Nanoparticle Supply limited

Current Achievements Have a thorough understanding of TNF and other cell membrane permeability factors, and antibody-nanoparticle interactions Conducted tests on nanoparticles in conjunction with electromagnets and magnetometers Determined most effective electromagnet design Have recorded observations on nanoparticles and their properties

Future Objectives Conduct experiments on mice tumors using nanoparticles Continue to explore innovative methods of testing our design Become more familiar with real-time imaging of the procedure(CCD, fluoroscopy) Revise IWB to reflect recent progress; finish designsafe Report our progress to Dr. Zhang, Georgia Tech, and request feedback