Molecular mechanism of polymer dynamics and kinetics of solute transport in multicomponent systems

许多新药是利用多种材料制成的，为患者提供最佳的治疗效果。例如，一次每日片剂是通过用大量聚合物和其他药物添加剂压缩药物粉末来制备的。然而，添加剂会影响片剂的透水性和药物释放。在我们的实验室里，我们也在开发“智能”设备，这种设备可以感知疾病状态，从而调整给患者的药量。这类设备的应用之一是通过调节胰岛素的释放来控制糖尿病患者的血糖水平。在这些设备中，多个组件集成在一个系统中。为了设计这样一种设备，并以高质量和低成本每天一次片剂，我们必须彻底了解聚合物的性质以及它们与其他成分和溶剂的相互作用，并拥有强大的计算工具来预测片剂或设备的性能。然而，到目前为止，通过建模来预测这类系统的分子机制和药物释放动力学还处于起步阶段，这阻碍了根据患者的需要开发新的药物产品，降低了医疗成本。因此，本项目旨在研究聚合物动力学的分子机制和溶质迁移动力学(1)在聚合物凝胶中；(2)在非均相可溶胀聚合物基质中；(3)在环境响应性聚合物复合膜中；以及(4)模拟和模拟非均相聚合物体系中的溶质迁移。聚合物基质将通过在模具中浇注聚合物和添加剂的混合物来制备。聚合物与添加剂和溶剂的相互作用将用各种现代技术来研究，包括热分析和荧光分析、分子成像和原子力显微镜。聚合物的溶胀、溶解和药物扩散的动力学将通过光学、电子和红外显微镜以及激光扫描图像分析来评估。溶质的扩散动力学将用溶解装置测定。将建立数学模型，并进行计算机模拟，以分析潜在的机理和预测药物释放动力学。

Many new medicines are formulated by using multiple materials to provide patients with optimal therapeutic benefits. For example, once daily tablets are prepared by compressing drug powders with a large amount of polymers and other pharmaceutical additives. The additives, however, would influence water penetration and drug release from the tablets. In our laboratory we are also developing "intelligent" devices that can sense disease state thus adjusting the amount of drug given to patients. One of applications of this type of devices is controlling sugar levels in diabetic patients by regulating insulin delivery. In these devices, multicomponents are integrated in one system. To design such a device and once daily tablets with good quality and low cost, we must have thorough understanding of the properties of polymers and their interaction with other ingredients and solvent and have powerful computational tools for prediction of the performance of the tablets or the devices. However, prediction of molecular mechanism and drug release kinetics in such systems by modeling remains in the infant stage so far, which hinders the development of new pharmaceutical products for patients' need and reduction in the cost of health care. This project is thus proposed to investigate molecular mechanism of polymer dynamics and kinetics of solute transport (1) in polymer gels; (2) in heterogeneous swellable polymer matrices; (3) in environment-responsive polymeric composite membranes; and (4) to model and simulate solute transport in heterogeneous polymer systems. The polymer matrices will be prepared by casting mixtures of polymers and additives in a mold. The interaction of polymers with additives and solvents will be studied with various modern techniques including thermal and fluorescence analyses, molecular imaging and atomic force microscopy. The dynamics of polymer swelling, dissolution and drug diffusion will be evaluated by optical, electronic and infra-red microscopy, and laser scanning image analysis. The diffusion kinetics of a solute will be determined using a dissolution apparatus. Mathematical model will be developed and computer simulation will be performed to analyze the underlying mechanism and to predict drug release kinetics.