In vitro and in vivo release of ciprofloxacin from osteoconductive bone defect filler.
OBJECTIVE
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.
Mäkinen
Tatu J
TJ
Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku, Medisiina B4, Kiinamyllynkatu 10, 20520 Turku, Finland.
Veiranto
Minna
M
Lankinen
Petteri
P
Moritz
Niko
N
Jalava
Jari
J
Törmälä
Pertti
P
Aro
Hannu T
HT
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D008297:Male; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D023421:Models, Animal; D010012:Osteogenesis; D010019:Osteomyelitis / Q000188:drug therapy* / Q000601:surgery; D011098:Polyglactin 910; D011817:Rabbits; D011859:Radiography
D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D011098:Polyglactin 910; D002939:Ciprofloxacin