AMINO ACID CONTAINING POLYANHYDRIDES AND PROTEIN RELEASE

储集层，整体，可膨胀和可侵蚀的聚合物体系已经被 旨在以受控的速度释放药物。后一种系统具有 因为可降解聚合物不必 一旦植入就会被移除，许多生物相容的聚合物都是已知的。 另一方面，包括多肽在内的各种生物活性物质 通过基因工程变得可用，繁殖出大量的 有兴趣开发有效管理它们的方法 人体。因此，该项目的长期目标是开发一种 基于新型聚酸酐的可腐蚀聚合物载体，可 用来以可预测的速度释放多肽和蛋白质 在动物和人类身上植入。具体目标是：1) 配制各种聚酸酐-蛋白质基质；2)孵化 这些基质在水介质中，在严格控制的条件下 PH、温度和搅拌，以确定聚合物的速率 降解和蛋白质释放。方法将包括聚合物合成， 中间体和最终产品的广泛表征，以及 用压缩模型法或溶剂法配制聚合物药物骨架 选角。孵化，然后进行实验，在其中所有的 感兴趣的物种将使用各种分析方法进行量化 技巧。这些研究将导致建立一个 聚合物降解/释药的定量机理模型 工艺，这些工艺将被用来在更多的 理性的基础。所获得的结果也将被用于制作 关于这些基质在控制释放中的有用性的预测 应用，并将成为未来体内研究的基础。

Reservoir, monolithic, swellable and erodible polymeric systems have been designed to release drugs at controlled rates. The latter system has gained increasing acceptance because degradable polymers do not have to be removed once implanted, and many biocompatible polymers are known. On the other hand, a variety of bioactive agents including peptides have become available through genetic engineering, spawning as great deal of interest in developing methods for administering them efficiently to the human body. Thus, the long-term goal of this project is to develop an erodible polymeric support based on novel polyanhydrides which could be used to release peptides and proteins at predictable rates after implantation in animals and humans. The specific aims are: 1) to formulate various polyanhydride-protein matrices; and 2) to incubate these matrices in aqueous media under carefully controlled conditions of pH, temperature, and agitation in order to determine the rates of polymer degradation and protein release. Methods will include polymer synthesis, extensive characterization of intermediates and final product, and formulation of polymer-drug matrices by compression modeling or solvent casting. Incubation, experiments will then be conducted in which all the species of interest will be quantified using a variety of analytical techniques. These studies will lead to the establishment of a quantitative mechanistic model of the polymer degradation/drug release processes, which will be used in turn to design these polymers on a more rational basis. The results obtained will also be used to make predictions on the usefulness of these matrices in controlled release applications, and will be the basis for future in vivo studies.