Block co-polymers combining synthetic aqnd biologically based blocks

在生物医学应用中经常使用的“塑料”--嵌段聚氨酯，是由软段和硬段交替不相容的“块”组成的。在之前由NSERC支持的工作中，我们已经生产了一系列这种聚氨酯，专门设计用于包含聚合物中对软组织中自然出现的分子酶的分解敏感的部位。我们将这些位置放在聚氨酯的硬段中，这是独一无二的，因为嵌段聚氨酯的降解通常是通过软段控制的。在这项应用中，我们建议将注意力转向软段，并加入通过重组DNA技术产生的天然蛋白质“片段”(多肽)。具体地说，我们将使用一种基于弹性蛋白的多肽。弹性蛋白存在于动脉等有弹性、可伸展的组织中，具有自发自组装成非常小的颗粒和纤维的特性。利用弹性蛋白作为软段或“塑料”，我们将能够控制聚氨酯的力学性能、降解率和生物影响。在第二部分中，我们建议通过设计和表征一系列新型弹性蛋白多肽/聚乙二醇嵌段共聚物系统来扩展弹性蛋白样多肽技术，以产生可用于广泛药物递送应用的不同结构。嵌段共聚物根据亲水(亲水)和疏水(憎水)嵌段的比例形成不同的结构。聚乙二醇是亲水的，弹性蛋白多肽是讨厌水的。有限数量的研究着眼于使用基于生物的共聚体系。重组技术可以用来生产形成不同结构的嵌段共聚物，这些结构具有对药物释放应用重要的特性。此外，这些聚合物系统很可能是生物相容的，可能会对温度做出反应，并被修饰以将药物输送到特定部位。这项工作将资助三名研究生、两名博士和一名硕士以及几名本科生论文。

Segmented polyurethanes, "plastics" frequently used in biomedical applications, are composed of alternating incompatible "blocks" of soft and hard segments. In work previously supported by NSERC,we have produced a family of these polyurethanes specifically designed to contain sites within the polymer that are sensitive to breakdown by molecules that occur naturally in soft tissue, enzymes. We put these sites in the hard block of the polyurethane, unique because the degradation of segmented polyurethanes is typically controlled via the soft block. In this application we propose to turn our attention to the soft segment and incorporate a naturally based protein "fragment" (polypeptide) produced via recombinant DNA technology. Specifically we will use a polypeptide based on the protein elastin. Elastin is found in elastic, extensible tissues such as arteries and has the quality of spontaneous self assembly into very small particles and fibers. In utilising the elastin as the soft segment or the "plastic", we will be able to control the mechanical properties, degradation rate and biological impact of the polyurethane. In part 2, we propose to expand the elastin-like polypeptide technology by designing and characterising a family of novel elastin polypeptide/polyethylene glycol block copolymer systems to produce different structures that can be used in a wide variety of drug delivery applications. Block copolymers form different structures depending on the proportion of hydrophilic (water loving)to hydrophobic(water hating)blocks. Polyethylene glycol is water loving and the elastin-peptide is water hating. A limited number of studies have looked at using biologically based copolymer systems. Recombinant techniques could be used to produce block copolymers that form different structures with characteristics important to in drug release applications. In addition, these polymer system would likely be biocompatible, could potentially respond to temperature and be modified to target the drug delivery to a specific site. Three graduate students, two Ph.D's and one masters as well as several undergraduate thesis students will be supported by this work.