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JAC Advance Access published online on October 18, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki366
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received May 22, 2005
Revised August 14, 2005
Accepted September 13, 2005

Original article

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

Tatu J. Mäkinen 1, Minna Veiranto 2, Petteri Lankinen 1, Niko Moritz 1, Jari Jalava 3, Pertti Törmälä 2, and Hannu T. Aro 1*

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

* To whom correspondence should be addressed.
Hannu T. Aro, E-mail: hannu.aro{at}utu.fi


  Abstract

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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