title: In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment.
abstract: The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, Orthopaedic Research Unit, University of Turku, Turku, Finland.
authors.forename: Jyri K
authors.initials: JK
authors.lastname: Koort
authors.forename: Esa
authors.initials: E
authors.lastname: Suokas
authors.forename: Minna
authors.initials: M
authors.lastname: Veiranto
authors.forename: Tatu J
authors.initials: TJ
authors.lastname: Mäkinen
authors.forename: Jari
authors.initials: J
authors.lastname: Jalava
authors.forename: Pertti
authors.initials: P
authors.lastname: Törmälä
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Aro
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018786:Bone Substitutes; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D008297:Male; D010019:Osteomyelitis / Q000188:drug therapy*; D011817:Rabbits
chemical_list: D000890:Anti-Infective Agents; D018786:Bone Substitutes; D002939:Ciprofloxacin