DIFFUSION FROM POLYMER SPHERES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 近年来，聚合物微球被广泛用作药物在体内缓释的骨架。为了模拟和随后控制这一过程，需要观察药物分布和监测球体内、制备后和释放过程中的物理条件的工具。目前用于这类测量的主要工具是激光扫描共聚焦荧光显微镜，它使用荧光标记药物。这种方法的问题是它不能深入到球体内，它提供的图像强度是非线性的(由于球体内的吸收和散射系数未知)，并且在体外/体内释放过程中不容易使用。此外，荧光不能很好地量化球体的孔隙率和球体中分子的自扩散张量。然而，ESR显微镜是我们实验室发展起来的一种新的磁共振成像方法，它具有解决光学方法的问题和局限性的潜力。这一分项目的目的是演示通过ESR显微镜可获得的额外信息的一个例子。在这项工作中，我们用ESR显微镜观察了几种典型尺寸为100微米的聚合物微球，这些微球内含稳定的有机自由基。这些微球是在新加坡大学王振华教授的团队中为我们准备的。通过我们的技术，我们监测了释放过程中的3D自由基分布，并测量了典型分辨率为~10微米的自由基的空间分辨T2。我们发现T2在球体内显著缩短，并将此观察到的结果归因于粘度的增加(可能是由于球体内聚乙二醇组分的存在)。沿着这些思路进行的进一步研究将有助于通过当前的理论解释释放过程的动力学，并可能开发出更好的微球制备方法以实现更好的控制释放。

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.