title: Synthesis and characterization of a novel biodegradable antimicrobial polymer.
abstract: Bacterial infection is a frequent complication associated with the use of medical devices. In an effort to address this problem, antibacterial agents have been incorporated or applied directly onto the surfaces of numerous types of medical devices. This study assessed the feasibility of using a novel biodegradable polymer to release antibiotic drugs in response to inflammatory related enzymes. A model drug polymer was synthesized using 1,6-hexane diisocyanate (HDI), polycaprolactone diol (PCL), and a fluoroquinolone antibiotic, ciprofloxacin. Polymers were characterized by size-exclusion chromatography (SEC), and elemental analysis. Biodegradation studies were carried out by incubating the polymers with solutions of cholesterol esterase (CE) or phosphate buffer (pH 7.0) for 30 days at 37 degrees C. The degradation was assessed by high-performance liquid chromatography (HPLC), mass spectrometry (MS) and 14C radiolabel release. Subsequently, the activity of the released antibiotic was assessed against a clinical isolate of Pseudomonas aeruginosa. HPLC analysis showed the release of multiple degradation products which were identified, by tandem MS, to include ciprofloxacin and derivatives of ciprofloxacin. The microbiological assessment showed that the released ciprofloxacin possessed antimicrobial activity; 1 microg/ml was measured after 10 days. The results of this study suggest that these novel bioresponsive antimicrobial polymers or similar analogs show promise for use in the control of medical device associated infections.
authors.affiliation: Department of Chemical Engineering and Applied Chemitry, Faculty of Engineering, University of Toronto, Ontario, Canada.
authors.forename: G L
authors.initials: GL
authors.lastname: Woo
authors.forename: M W
authors.initials: MW
authors.lastname: Mittelman
authors.forename: J P
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D005240:Feasibility Studies; D013058:Mass Spectrometry; D008422:Materials Testing; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C412586:poly(1,6-hexanediisocyanate-co-polycaprolactonediol-co-ciprofloxacin); D002939:Ciprofloxacin; D002787:Sterol Esterase