- 3:15 PM

Magnetic Resonance Imaging Contrast Agents for Monitoring Drug Delivery in Vivo

Rozamond Y. Sweeney and Mark E. Davis. Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., MC 210-41, Pasadena, CA 91125

Therapeutic nanoparticles are designed to deliver drugs to designated tissues or cells while minimizing accumulation in non-target tissues. Real time imaging of therapeutic nanoparticles can potentially monitor the in vivo distribution and pharmacokinetic properties of a drug delivery system. In principle, imaging techniques should provide verification that a drug is accumulating in the desired tissue. Our group has designed cyclodextrin polymers to interact with nucleic acids or small molecule drugs to form therapeutic nanoparticles and one variant is currently in human clinical trials. Here, magnetic resonance imaging (MRI) contrast agents that have the same size and surface properties as the therapeutic cyclodextrin nanoparticles are prepared. Superparamagnetic iron oxide nanoparticles are coated in cyclodextrin polymers and when made ca. the same diameter as a commercially available MRI contrast agent (Feridex), are found to have similar magnetic properties. The surface of the contrast agents can be easily modified to display a cell-surface receptor targeting ligand. The contrast agents should have similar in vivo localization as the therapeutic nanoparticles because of their similar size, charge, and targeting ligands and not have the side effects associated with Feridex. Studies are currently ongoing to image the in vivo distribution of the contrast agents by MRI with the goal of determining the optimal size and surface properties necessary for targeting tumors and avoiding reticuloendothelial cell uptake. We will present the preparation methods and MRI results from systemic injections of these nanoparticles in mice.