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Gatifloxacine (GFLX)-containing poly(lactide-co-glycolide) (PLGA) was introduced to the pores and surfaces of porous β-tricalcium phosphate (βTCP) granules by melt compounding whereby no toxic solvent was used. The granular composite of GFLX-loaded PLGA and βTCP released GFLX for 42 days in Hanks' balanced solution and exhibited sufficient in vitro bactericidal activity against Streptococcus milleri and Bacteroides fragilis for at least 21 days. For in vivo evaluation, the granular composite was implanted in the dead space created by the debridement of osteomyelitis lesion induced by S. milleri and B. fragilis in rabbit mandible. After a 4-week implantation, the inflammation area within the debrided area was markedly reduced accompanied with osteoconduction and vascularization in half of the rabbits, and even disappeared in one of the six rabbits without any systemic administration of antibiotics. Outside the debrided area, inflammation and sequestrum were observed but the largest of such affected areas amounted to only 0.125 times of the originally infected and debrided area. These findings showed that the granular composite was effective for the local treatment of osteomyelitis as well as an osteoconductive scaffold which supported and encouraged vascularization.

A composite of co-polymer of lactic and glycolic acids (PLGA) loaded with gatifloxacine (GFLX), an antibiotics, and a β-tricalcium phosphate (βTCP) porous ceramic body was prepared by a solvent-free process in which no toxic solvent was used. The GFLX-loaded PLGA released GFLX for 8 weeks in Hanks’ balanced solution. The inhibitory zone diameter (26.25±0.95 mm) for GFLX-containing PLGA disk against S. milleri was significantly larger than 18 mm, and comparable to that (24.88±1.6 mm) for the KB paper disk containing 5 μg of GFLX/disk. This means that the GFLX-containing PLGA has the clinical efficacy. The molten PLGA containing GFLX was successfully loaded in the pores and on the surface of the porous βTCP ceramic at 120 °C at a reduced pressure of 0.02 MPa. The composite of GFLX-loaded porous βTCP ceramic would be promising for treating osteomyelitis.

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