RESUMO
Molten 10 wt% gatifloxacine (GLFX-loaded poly(lactide-co-glycolide) (PLGA) was introduced into three-dimensionally interconnected pores and onto the surfaces of hydroxyapatite (HA) granules. The composite granules exhibited clinically sufficient bactericidal activities against Streptococcus milleri and Bacteroides fragilis from 3 h to 10 days. The composite granules were implanted in bone defects created by debridement of osteomyelitis lesions in rabbit mandibles. After 4-week implantation, inflammation in the composite granule-implanted group was significantly smaller than that in the debridement group (p<0.05). Moreover, newly formed bone was observed in the pores and on the surface of HA granules of the composite. These findings show that GFLX/HA composite controls bacterial infection and supports bone regeneration for osteomyelitis treatment.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Fluoroquinolonas/química , Fluoroquinolonas/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Mandíbula/cirurgia , Osteomielite/tratamento farmacológico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Animais , Bacteroides fragilis/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Desbridamento , Portadores de Fármacos , Durapatita/química , Durapatita/farmacologia , Gatifloxacina , Concentração de Íons de Hidrogênio , Teste de Materiais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Coelhos , Streptococcus milleri (Grupo)/efeitos dos fármacosRESUMO
Composites of gatifloxacin (GFLX)-loaded poly (lactic-co-glycolic) acid (PLGA) and ß-tricalcium phosphate (ßTCP) containing 0, 1, and 10 wt % GFLX (0, 1, and 10 wt % GFLX composites), and GFLX-loaded PLGA containing 1, 5, and 10 wt % GFLX (1, 5, and 10wt % GFLX-PLGA) as controls were fabricated and characterized in vitro and in vivo. On in vitro evaluation, the 10 wt % GFLX composite released GFLX over at least 28 days in Hanks' balanced solution and exhibited clinically sufficient bactericidal activities against Streptococcus milleri and Bacteroides fragilis from 1 h to 10 days. The 0, 1, and 10 wt % GFLX composites and 10 wt % GFLX-PLGA were implanted in bone defects created by debridement of osteomyelitis lesions induced by S. milleri and B. fragilis in the mandible of rabbits (n = 5). Four weeks after implantation of the 10 wt % GFLX composite, inflammation in the debrided area disappeared in all the rabbits, while inflammation remained in all the rabbits after implantation of the 0 wt % GFLX composite and 10 wt % GFLX-PLGA, and in three rabbits after implantation of the 1 wt % GFLX composite. Bone formation appears to be less intense for the 10 wt % GFLX composite than for the 1 wt % GFLX composite probably owing to the rapid degradation of the 10 wt % GFLX composite. These findings show that the GFLX composite is effective for the local treatment of osteomyelitis.