Design of infection-resistant antibiotic-releasing polymers: I. Fabrication and formulation

Biomaterials-related infections are often observed with prosthetic implants and in many cases result in the failure of the devices. To design a biomed ically useful polymer that is intrinsically infection-resistant, we have de veloped a ciprofloxacin-loaded polyurethane (PU) matrix that releases antib iotic locally at the implant surface, thereby minimizing bacterial accumula tion. We report here the methods of fabrication and formulation for making such antibiotic-loaded devices, as well as evidence of their bactericidal p roperties. Specifically, various pore-forming agents and drug loadings were examined. An optimum formulation consisting of BIOSPAN(R) PU, poly(ethylen e glycol) and ciprofloxacin offered the longest effective period of sustain ed release (5 days). The bactericidal efficacy of the released ciprofloxaci n against Pseudomonas aeruginosa (PA) was four times that of the control PU without antibiotics. This bactericidal efficiency was due to an increase i n 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 possib ility of biofilm-related infection. (C) 1999 Elsevier Science B.V. All righ ts reserved.