title: Design of infection-resistant antibiotic-releasing polymers: I. Fabrication and formulation.
abstract: Biomaterials-related infections are often observed with prosthetic implants and in many cases result in the failure of the devices. To design a biomedically useful polymer that is intrinsically infection-resistant, we have developed a ciprofloxacin-loaded polyurethane (PU) matrix that releases antibiotic locally at the implant surface, thereby minimizing bacterial accumulation. We report here the methods of fabrication and formulation for making such antibiotic-loaded devices, as well as evidence of their bactericidal properties. Specifically, various pore-forming agents and drug loadings were examined. An optimum formulation consisting of BIOSPAN PU, poly(ethylene glycol) and ciprofloxacin offered the longest effective period of sustained release (5 days). The bactericidal efficacy of the released ciprofloxacin against Pseudomonas aeruginosa (PA) was four times that of the control PU without antibiotics. This bactericidal efficiency was due to an increase in the PA detachment from the surface. These observations suggested that the released ciprofloxacin was biologically active in preventing the bacteria from permanently adhering to the substratum, and thus decreasing the possibility of biofilm-related infection.
authors.affiliation: Department of Chemical Engineering, Box 351750, University of Washington, Seattle 98195, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Kwok
authors.forename: C
authors.initials: C
authors.lastname: Wan
authors.forename: S
authors.initials: S
authors.lastname: Hendricks
authors.forename: J D
authors.initials: JD
authors.lastname: Bryers
authors.forename: T A
authors.initials: TA
authors.lastname: Horbett
authors.forename: B D
authors.initials: BD
authors.lastname: Ratner
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D017053:Infection Control / Q000379:methods; D011140:Polyurethanes / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D011140:Polyurethanes; D002939:Ciprofloxacin