In vitro and in vivo release of ciprofloxacin from osteoconductive bone defect filler

OBJECTIVES: Impregnation of antimicrobial agents within biodegradable carriers with osteoconductive properties could provide the means for one-stage surgical treatment of osteomyelitis. In this study, the in vitro and in vivo antibiotic release from this type of bone defect filler was characterized. METHODS: Cylindrical pellets (2.5 x 1.5 mm) were manufactured from bioabsorbable poly(L-lactide-co-glycolide) (PLGA) matrix, ciprofloxacin [8.3 +/- 0.1% (w/w)] and osteoconductive bioactive glass microspheres (90-125 microm) [27 +/- 2% (w/w)]. In vitro studies were carried out to delineate the release profile of the antibiotic. The antimicrobial activity of the release antibiotic was verified with MIC testing. In a time-sequence study in the rabbit, pellets were surgically implanted in the proximal tibia and the antibiotic concentrations achieved in bone were measured at 1, 2, 3, 4, 5 and 6 months. RESULTS: In vitro elution studies showed sustained release of ciprofloxacin at a therapeutic level (>2 microg/mL) over a time period of 4 months. The released ciprofloxacin had maintained its antimicrobial capacity against five standard ATCC strains. In vivo, the delivery system produced high local bone concentrations (247.9 +/- 91.0 mug/g of bone) for a time period of 3 months with no significant systemic exposure. Histomorphometry and micro-CT imaging confirmed new bone formation around the pellets within 3 months as a sign of an independent osteoconductive property of the composite. CONCLUSIONS: The tested composite seems to be a promising option for local therapy of surgically treated bone infections. The main advantages are the antibiotic release for a definite time period with therapeutic concentrations, which may minimize slow residual release at suboptimal concentrations.