AMINO ACID CONTAINING POLYANHYDRIDES AND PROTEIN RELEASE

储层、整体、可膨胀和可腐蚀聚合物体系

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.