Electron spin resonance microscopy applied to the study of controlled drug release

We describe our recent developments towards 3D micron-scale imaging capability, based on electron spin resonance (ESR), and its application to the study of controlled release. The method, termed ESR microscopy (ESRM), is an extension of the conventional "millimeter-scale" ESR imaging technique. It employs paramagnetic molecules (such as stable radicals or spin-labeled drugs) and may enable one to obtain accurate 3D spatially resolved information about the drug concentration, its self-diffusion tensor, rotational correlation time and the pH in the release matrix. Theoretical calculations, along with initial experimental results, suggest that a 3D resolution of approximately 1 microm is feasible with this method. Here we were able to image successfully a high spin concentration sample with a resolution of approximately 3 x 3 x 8 microm and subsequently study a single approximately 120 microm biodegradable microsphere, internalized with a dilute solution of trityl radical, with a resolution of approximately 12.7 x 13.2 x 26 microm. Analysis of the microsphere ESR imaging data revealed a likely increase in the viscosity inside the sphere and/or binding of the radical molecule to the sphere matrix. Future directions for progress are also discussed.