This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recently, there has been an extensive use of polymeric microspheres as a matrix for the slow release of drugs inside the body. To model and subsequently control this process, one requires tools for observing the drug distribution and monitoring the physical conditions within the sphere, after preparation, and during the release process. Currently the major tool used for such measurements is laser scanning confocal fluorescence microscopy, which employs fluorescent labeled drugs. The problems with this method are that it does not enable to penetrate deep into the sphere, it provides non-linear image intensity (due to unknown absorption and scattering coefficients in the sphere), and it cannot be employed easily during the in-vitro/in-vivo release process. Furthermore fluorescence does not have a good capability to quantify the porosity of the spheres, and the self diffusion tensor of the molecules in the sphere. ESR microscopy, however, which is a new magnetic resonance imaging method developed in our lab, has a potential of answering the problems and limitations of optical methods. This subproject is aimed at demonstrating an example for the additional information available through ESR microcopy. In this work, we have examined by ESR microscopy several types of polymer microspheres with a typical size of 100 microns, internalized with stable organic radicals. These microspheres were prepared for us at the University of Singapore in the group of Prof. C. H. Wang. We monitored, through our technique, the 3D radical distribution during the release process and measured the spatially resolved T2 of the radicals with a typical resolution of ~ 10 microns. We have found that T2 was significantly shorter inside the sphere and attributed this observation to an increased viscosity (probably due to the presence of poly-ethylene-glycol inside the sphere). Further investigations along these lines would help to explain the kinetics of the release process through current theories, and may enable the development of better methods of sphere preparation for more controlled release.
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