Block co-polymers combining synthetic aqnd biologically based blocks

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Segmented polyurethanes, "plastics" frequently used in biomedical applications, are composed of alternating incompatible "blocks" of soft and hard segments. In work previously supported by NSERC,we have produced a family of these polyurethanes specifically designed to contain sites within the polymer that are sensitive to breakdown by molecules that occur naturally in soft tissue, enzymes. We put these sites in the hard block of the polyurethane, unique because the degradation of segmented polyurethanes is typically controlled via the soft block. In this application we propose to turn our attention to the soft segment and incorporate a naturally based protein "fragment" (polypeptide) produced via recombinant DNA technology. Specifically we will use a polypeptide based on the protein elastin. Elastin is found in elastic, extensible tissues such as arteries and has the quality of spontaneous self assembly into very small particles and fibers. In utilising the elastin as the soft segment or the "plastic", we will be able to control the mechanical properties, degradation rate and biological impact of the polyurethane. In part 2, we propose to expand the elastin-like polypeptide technology by designing and characterising a family of novel elastin polypeptide/polyethylene glycol block copolymer systems to produce different structures that can be used in a wide variety of drug delivery applications. Block copolymers form different structures depending on the proportion of hydrophilic (water loving)to hydrophobic(water hating)blocks. Polyethylene glycol is water loving and the elastin-peptide is water hating. A limited number of studies have looked at using biologically based copolymer systems. Recombinant techniques could be used to produce block copolymers that form different structures with characteristics important to in drug release applications. In addition, these polymer system would likely be biocompatible, could potentially respond to temperature and be modified to target the drug delivery to a specific site. Three graduate students, two Ph.D's and one masters as well as several undergraduate thesis students will be supported by this work.