The objective of this proposal is the development of degradable, transducible, biocompatible, elastomeric matrices to function as drug delivery systems. Despite continuing interest in the development of polymers, both synthetic and natural, (over a 25-year period), there is yet a need for suitable materials for drug delivery. Such materials would have significant and broad clinical applications including continuous and/or localized delivery of existing therapeutic agents as well as delivery systems for the new proteinaceous agents resulting from genetic engineering. The elastomeric polypeptides utilized in this work are a unique class of polymers designed from repeat sequences which occur in native elastin. These materials are particularly suited for this application since they are constructed of natural amino acids arranged in sequences which occur throughout the body. All data to date, including the eleven recommended generic biological tests, as well as muscle and intraperitoneal implant studies, indicate the parent polypentapeptide and its gamma-irradiated cross-linked matrix to be biocompatible and totally innocuous. Our understanding of the science of these materials has progressed to the point that polymers can be designed which exhibit a set of specified physical characteristics. Initial results indicate that the rate of degradation and/or swelling of these matrices could be modulated by the inclusion of various chemical clocks located both within the backbone and side chains. Phase I of this proposal will produce monolith slabs and nanospheres and will extend the in vitro studies on controlling the rate of degradation and release of therapeutic agents from these matrices. Phase II will involve studies of degradation and agent release in animal models and biological testing of the materials developed in Phase I.
