AMINO ACID CONTAINING POLYANHYDRIDES AND PROTEIN RELEASE

储层、整体、可溶胀和可侵蚀的聚合物系统已经被 以受控的速率释放药物 后一种系统具有 由于可降解聚合物不必 一旦植入就被移除，并且已知许多生物相容性聚合物。 另一方面，包括肽在内的多种生物活性剂具有生物活性。 通过基因工程变得可用， 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个 基于新型聚酸酐的可侵蚀聚合物载体， 用于以可预测的速率释放肽和蛋白质， 植入动物和人体。 具体目标是：1） 配制各种聚甘露糖-蛋白质基质;和2）孵育 这些基质在水介质中在仔细控制的条件下， 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 通过压缩成型或溶剂法配制聚合物-药物基质 铸造 孵化，然后将进行实验，其中所有的 感兴趣的物种将使用各种分析方法进行定量。 技术. 这些研究将导致建立一个 聚合物降解/药物释放的定量机理模型 工艺，这将反过来用来设计这些聚合物上更 理性基础 所获得的结果也将用于 预测这些基质在控制释放中的有用性 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.