Development of novel biodegradable antimicrobial polymers for biomaterials applications

grantor: University of TorontoBacterial infection is a frequent complication associated with the use of medical devices. Antimicrobial agents have been incorporated into or applied directly onto the surfaces of devices to combat infection. This thesis will assess the feasibility of using a novel biodegradable polymer to release antibiotic drugs in response to inflammatory related enzymes. A series of biodegradable drug polymers were synthesized using diisocyanates, oligomeric compounds, and an antibiotic, ciprofloxacin. The drug polymers were characterized by gel permeation chromatography (GPC), and elemental analysis. Biodegradation studies were carried out by incubating the polymers with solutions of cholesterol esterase (CE). Degradation was assessed by high performance liquid chromatography (HPLC), mass spectrometry (MS) and radiolabel release. Subsequently, the activity of the released antibiotic was assessed against a clinical isolate of Pseudomonas aeruginosa. For one of the polymer formulations, the release of ciprofloxacin was approximately two-fold higher in the presence of enzyme as compared to buffer alone. Another formulation using a different diisocyanate showed the release of multiple degradation products. The results of this study suggest that these novel antimicrobial polymers or similar analogs show good potential for use in the control of medical device associated infections.M.A.Sc