A1 Refereed original research article in a scientific journal

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




AuthorsMakinen TJ, Veiranto M, Lankinen P, Moritz N, Jalava J, Tormala P, Aro HT

PublisherOXFORD UNIV PRESS

Publication year2005

JournalJournal of Antimicrobial Chemotherapy

Journal name in sourceJOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Journal acronymJ ANTIMICROB CHEMOTH

Volume56

Issue6

First page 1063

Last page1068

Number of pages6

ISSN0305-7453

DOIhttps://doi.org/10.1093/jac/dki366


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 mu m) [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 mu g/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 mu g/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.



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