AMINO ACID CONTAINING POLYANHYDRIDES AND PROTEIN RELEASE

含氨基酸的聚酐和蛋白质释放

• 批准号: 6240044
• 负责人: CARLOS A RAMFREZ
• 金额: $ 7.08万
• 依托单位: UNIVERSITY OF PUERTO RICO MAYAGUEZ
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240044
• 关键词: aminoacid; animal tissue; biological transport; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; drug delivery systems; drug interactions; high performance liquid chromatography; peptide chemical synthesis; polymers; proteolysis; radioimmunoassay

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.

储层，整体，可膨胀和可侵蚀的聚合系统已经是 旨在以受控速率释放药物。 后一个系统具有 由于可降解的聚合物不必必须 植入一旦植入，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 通过基因工程来获得，产卵很大 对开发方法有效管理方法的兴趣 人体。 因此，该项目的长期目标是开发 基于新型多丙二醇的侵蚀性聚合物支持，这可能是 用于以可预测速率释放肽和蛋白质 植入动物和人类。 具体目的是：1） 制定各种多苯胺 - 蛋白质基质； 2）孵化 在仔细控制的条件下，这些矩阵 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 通过压缩建模或溶剂制定聚合物 - 药物矩阵 铸件。 然后将进行孵育，然后进行实验 感兴趣的物种将通过各种分析来量化 技术。 这些研究将导致建立 聚合物降解/药物释放的定量机械模型 工艺将依次用于设计这些聚合物 理性的基础。 获得的结果也将用于使 对这些矩阵在受控释放中的实用性的预测 应用，将成为未来体内研究的基础。