DIFFUSION FROM POLYMER SPHERES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 近年来，聚合物微球作为体内药物缓释的基质得到了广泛的应用。 为了模拟并随后控制该过程，需要用于观察药物分布和监测球体内、制备后和释放过程期间的物理条件的工具。 目前，用于这种测量的主要工具是激光扫描共聚焦荧光显微镜，它采用荧光标记的药物。 这种方法的问题在于，它不能深入穿透到球体中，它提供非线性图像强度（由于球体中未知的吸收和散射系数），并且它不能在体外/体内释放过程中容易地使用。 此外，荧光没有很好的能力来量化球的孔隙率，以及球中分子的自扩散张量。然而，ESR显微镜是我们实验室开发的一种新的磁共振成像方法，具有回答光学方法的问题和局限性的潜力。 该子项目旨在展示通过ESR显微镜获得的额外信息的示例。 在这项工作中，我们研究了ESR显微镜几种类型的聚合物微球的典型尺寸为100微米，内化与稳定的有机自由基。 这些微球是由新加坡大学的C. H.王. 我们监测，通过我们的技术，在释放过程中的3D自由基分布和测量的空间分辨T2的自由基的典型分辨率为~ 10微米。 我们已经发现，T2在球体内明显较短，并将这一观察结果归因于粘度增加（可能是由于球体内存在聚乙二醇）。 沿着这些路线的进一步研究沿着将有助于通过当前的理论解释释放过程的动力学，并可能使更好的方法的球体制备的更多的控制释放的发展。

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.