(543d) Magnetic Resonance Imaging of Drug Release From 3D Poly(propylene fumarate) Scaffolds

Authors: 
Choi, J., Massachusetts Institute of Technology
Kim, K., Rice University
Liu, G., Kennedy Krieger Institute
Hyeon, T., Seoul National University
McMahon, M. T., Kennedy Krieger Institute
Fisher, J. P., University of Maryland
Gilad, A. A., Johns Hopkins University
Kim, T., Seoul National University


Implantable, three-dimensional (3D) polymer scaffolds have been drawing attention from various disciplines because of their unique properties.  Efficient drug delivery, with a controlled drug-release manner at the targeted site, is one of the major applications for polymer scaffolds in biomedical research.  The use of 3D poly(propylene fumarate) (PPF) scaffolds as a drug-release matrix is relatively new, but is a promising application in several aspects.  First of all, the highly porous structure of PPF scaffolds provides sizable drug-loading spaces.  Furthermore, a photo-crosslinked PPF scaffold is able to retain its initial porosity and mechanical properties for 18-32 weeks in vitro, and its degradability can be controlled by adjusting fabrication parameters, such as PPF molecular weight and photoinitiator content. Rapid improvements in magnetic resonance imaging (MRI) instrumentation and techniques have led to increased spatial resolution (up to 50-100 µm for rodent in vivo imaging).  In addition, a variety of novel nanoparticles designed for MRI can enhance the MRI contrast  even further, making it possible to image cellular and molecular events non-invasively and co-register these events with 3D anatomical structures.  Here we report on the use of porous PPF scaffolds loaded with doxorubicin (DOX)-coated iron oxide and manganese oxide nanoparticles as a vehicle for sustained anti-cancer drug release. Using nanoparticles as a drug carrier contributes to more efficient loading of drug molecules onto the PPF scaffold. It also allows monitoring the release of drug-nanoparticle complexes from the PPF scaffold surface via changes in MRI contrast and absorption spectra in a media containing scaffold pieces. In addition, as a proof-of-concept experiment, it was demonstrated that the diamagnetic CEST contrast agent, protamine sulfate (PS), can also be used directly, without nanoparticle carriers, to monitor release from the PPF scaffolds by MRI. This report about drug-delivering 3D PPF scaffolds, with a sustained release rate and bimodal imaging (fluorescence and magnetic resonance) capabilities, suggests this new system may potentially be used in various biomedical applications.