STRUCTURAL ENCAPSULATION OF MODEL PROTEINS IN BIOPOLYMER

描述(改编自应用)：许多蛋白质，包括 与药物相关的药物，可以从 人工合成的生物相容聚合物对人体。这些发现保持了 承诺大幅扩大此类蛋白质的使用，以预防 以及疾病的治愈。然而，蛋白质在生物相容性中的包封性 聚合物包括对其结构有害的事件，如接触 有机溶剂、剪切力、疏水界面和脱水。而当 从这种装置分析蛋白质的释放动力学是常规的， 申请者最近提供了关于蛋白质的第一个结构数据 生物相容聚合物。这项建议的总体目标是将 新开发的光谱方法，以进一步合理化的影响 包埋条件对模型蛋白结构的影响及相关研究 具有发布和稳定性数据的结构。最终的目标是理解 蛋白质包埋后的结构和稳定性 生物相容聚合物提供合理的配方策略。为此， 他们将主要使用傅里叶变换红外(FTIR)光谱来 定量描述模型二级结构的变化 蛋白质在其包裹的不同阶段。此外，高分辨率 H/D交换核磁共振波谱将用于获得互补的结构 数据。结构数据将与稳定性参数相关联，例如 从设备中累积释放的蛋白质及其特异性 生物活性。他们将特别专注于优化 非水胶囊化方法，在那里他们已经实现了 两种模型蛋白(重组人生长激素)的结构保存 和牛血清白蛋白)在FDA批准的封装中 聚(乳酸-羟基乙酸)酸。此外，最常用的方法是 蛋白质包埋技术，即复乳化溶剂挥发技术，将 通过改变工艺参数进行了系统的分析。他们是 尤其对稳定蛋白质中的有害物质感兴趣 第一包埋步骤，其中形成水-有机溶剂界面 蛋白质溶液受到很高的剪切力。他们还将 解决构象问题。蛋白质在有机溶剂中的稳定性 在实验上，特别关注添加剂对其性能的影响 热稳定性。

Description (Adapted from Application): Many proteins, including pharmaceutically relevant ones, can be delivered for prolonged times from synthetic biocompatible polymers to the human body. These findings hold the promise of significantly expanding the use of such proteins for the prevention and cure of diseases. However, the encapsulation of proteins in biocompatible polymers includes events detrimental to their structure, such as exposure to organic solvents, shear forces, hydrophobic interfaces, and dehydration. While it is routine to analyze the release kinetics of proteins from such devices, the applicants recently provided the first structural data on proteins within biocompatible polymers. The overall objective of this proposal is to apply the newly developed spectroscopic methods to further rationalize the impact of the encapsulation conditions on the structure of model proteins and relate structural with release and stability data. The ultimate goal is to understand the structure and stability consequences of protein encapsulation in biocompatible polymers to provide rational formulation strategies. To this end they will primarily employ Fourier-transform infrared (FTIR) spectroscopy to quantitatively characterize changes in the secondary structure of model proteins at various stages of their encapsulation. In addition, high-resolution H/D exchange NMR spectroscopy will be applied to gain complementary structural data. The structural data will be correlated with stability parameters, such as cumulative release of the proteins from the devices and their specific biological activity. They will, in particular, concentrate on optimizing non-aqueous encapsulation approaches, where they have already achieved structural preservation of two model proteins (recombinant human growth hormone and bovine serum albumin) upon encapsulation in FDA-approved poly(lactic-co-glycolic)acid. In addition, the most common method used for protein encapsulation, the double emulsion solvent evaporation technique, will be systematically analyzed by variation of the processing parameters. They are particularly interested in the stabilization of proteins in the detrimental first encapsulation step, where an aqueous-organic solvent interface is formed and protein solutions are subjected to high shear forces. They will also address the conformational. Stability of proteins in organic solvents experimentally, particularly focussing on the influence of additives on their thermal stability.