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

许多新药是通过使用多种材料配制的，为患者提供最佳的治疗益处。例如，每日一次的片剂通过将药物粉末与大量聚合物和其它药物添加剂压制来制备。然而，添加剂会影响水渗透和药物从片剂中释放。在我们的实验室里，我们还在开发“智能”设备，可以感知疾病状态，从而调整给病人的药量。这种类型的设备的应用之一是通过调节胰岛素输送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。为了设计这样的装置和具有良好质量和低成本的每日一次的片剂，我们必须彻底了解聚合物的性质及其与其他成分和溶剂的相互作用，并具有用于预测片剂或装置的性能的强大计算工具。然而，迄今为止，通过模型化来预测此类系统中的分子机制和药物释放动力学仍然处于婴儿阶段，这阻碍了针对患者需求的新药物产品的开发和医疗保健成本的降低。因此，本项目提出研究聚合物动力学的分子机理和溶质传输动力学（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;和（4）建模和模拟非均相聚合物体系中的溶质传输。聚合物基质将通过在模具中浇铸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通过各种现代技术进行研究，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进行评价。溶质的扩散动力学将使用溶解装置测定。将建立数学模型并进行计算机模拟，以分析潜在的机制并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.