Injectable biodegradable polymers for local drug delivery

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This proposal is an extension of ongoing projects in my research group on the development of biodegradable, injectable polymers for localized protein drug delivery. A major research focus in my research group is the development of an effective formulation of angiogenic growth factors to stimulate blood vessel growth in tissues of low local oxygen concentration as well as the delivery of immunomodulators used to treat cancer. These protein therapeutics need to be present in the afflicted tissue for multiple weeks in order to be effective, and thus a polymeric controlled release vehicle is a suitable approach. To minimize patient trauma, we are focusing on an injectable, biodegradable delivery system. We have chosen a carbonate-based polymer as a building block for the preparation of new injectable formulations as they degrade but do not form the acidic degradation products that are problematic with the conventional aliphatic polyesters. The objectives of this proposal are to synthesize low molecular weight poly(trimethylene carbonate)-based polymers of low viscosity, incorporate angiogenic growth factors such as vascular endothelial growth factor as particles within them, assess the factors governing release of these growth factors in vitro, determine the bioactivity of these growth factors upon their release, and assess the in vitro degradation rates of the new polymers. To accomplish these objectives, the low molecular weight poly(trimethylene carbonate) prepolymers will be combined utilizing bonds that are readily cleavable in the body. The polymers will be characterized via gel permeation chromatography, nuclear magnetic resonance spectroscopy, rheology, and differential scanning calorimetry, both as prepared and during in vitro degradation. Growth factor release from the polymers will be measured using ELISA and bioactivity following release through cell-based proliferation assays already established in my laboratory. The significance of this work is that new, and potentially very useful, polymer biomaterials will be developed that could have a range of drug delivery applications.