Controlled release of vancomycin from Poloxamer 407 gels

The purpose of this study was to investigate Poloxamer 407 25% (w/w) formul ations aimed at prolonging the residence time of vancomycin, a time-depende nt antibiotic, in a body site with a high infectious risk. Reversible therm al gelation of the formulations permitted their local injection in liquid f orm and in situ gelation as they warmed to body temperature. Neither the rh eological properties of the Poloxamer matrices nor the antibacterial activi ty of vancomycin was altered by their combination. In vitro, the dispersed form exhibited prolonged release, with a lower diffusion coefficient of van comycin compared to the solubilized form (4.7 x 10(-8) vs 2.1 x 10(-7) cm(2 ) s(-1)). In rats, a single dose was well tolerated and resulted in a high local concentration for 24 h (>131 mg 1(-1) for the solubilized form), foll owed by lower but effective antibacterial levels for at least 8 days. Contr olled-release profiles, good preservation of vancomycin activity, good tole rability in rats, and ease of administration suggest that Poloxamer 407 may be useful as a vancomycin delivery vehicle for local prophylaxis of infect ions, especially in prosthetic surgery. (C) 1999 Elsevier Science B.V. All rights reserved.