Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones.
Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.
Woo
G L Y
GL
Department of Chemical Engineering and Applied Chemistry, Faculty of Engineering, University of Toronto, Toronto, Ontario, Canada.
Yang
M L
ML
Yin
H Q
HQ
Jaffer
F
F
Mittelman
M W
MW
Santerre
J P
JP
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry*; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000737:chemistry*; D051379:Mice; D009504:Neutrophils; D011108:Polymers
D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D011108:Polymers; D002939:Ciprofloxacin