PMID- 16234335 OWN - NLM STAT- MEDLINE DCOM- 20060321 LR - 20161124 IS - 0305-7453 (Print) IS - 0305-7453 (Linking) VI - 56 IP - 6 DP - 2005 Dec TI - In vitro and in vivo release of ciprofloxacin from osteoconductive bone defect filler. PG - 1063-8 AB - 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. FAU - Makinen, Tatu J AU - Makinen TJ AD - Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku, Medisiina B4, Kiinamyllynkatu 10, 20520 Turku, Finland. FAU - Veiranto, Minna AU - Veiranto M FAU - Lankinen, Petteri AU - Lankinen P FAU - Moritz, Niko AU - Moritz N FAU - Jalava, Jari AU - Jalava J FAU - Tormala, Pertti AU - Tormala P FAU - Aro, Hannu T AU - Aro HT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051018 PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Anti-Bacterial Agents) RN - 0 (Bone Substitutes) RN - 0 (Delayed-Action Preparations) RN - 34346-01-5 (Polyglactin 910) RN - 5E8K9I0O4U (Ciprofloxacin) SB - IM MH - Animals MH - Anti-Bacterial Agents/administration & dosage/analysis/pharmacokinetics/pharmacology MH - Bone Substitutes/*chemistry MH - Bone and Bones/chemistry/diagnostic imaging MH - Ciprofloxacin/*administration & dosage/analysis/*pharmacokinetics/pharmacology MH - Delayed-Action Preparations MH - Male MH - Microbial Sensitivity Tests MH - Microspheres MH - Models, Animal MH - Osteogenesis MH - Osteomyelitis/*drug therapy/surgery MH - Polyglactin 910 MH - Rabbits MH - Radiography EDAT- 2005/10/20 09:00 MHDA- 2006/03/22 09:00 CRDT- 2005/10/20 09:00 PHST- 2005/10/20 09:00 [pubmed] PHST- 2006/03/22 09:00 [medline] PHST- 2005/10/20 09:00 [entrez] AID - dki366 [pii] AID - 10.1093/jac/dki366 [doi] PST - ppublish SO - J Antimicrob Chemother. 2005 Dec;56(6):1063-8. doi: 10.1093/jac/dki366. Epub 2005 Oct 18.