JAC Advance Access originally published online on October 18, 2005
Journal of Antimicrobial Chemotherapy 2005 56(6):1063-1068; doi:10.1093/jac/dki366
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In vitro and in vivo release of ciprofloxacin from osteoconductive bone defect filler
1 Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku, Medisiina B4, Kiinamyllynkatu 10, 20520 Turku, Finland; 2 Institute of Biomaterials, Tampere University of Technology, PO Box 589, 33101 Tampere, Finland; 3 Department of Human Microbial Ecology and Inflammation, National Public Health Institute, PO Box 57, 20521 Turku, Finland
Received 22 May 2005; returned 25 July 2005; revised 14 August 2005; accepted 13 September 2005
* Corresponding author. Tel: +358-2-313-0000; Fax: +358-2-313-2284; E-mail: hannu.aro{at}utu.fi
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 µm) [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 µg/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 µg/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.
Keywords: antimicrobial delivery , bioactive glass , osteomyelitis
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