Ciprofloxacin implants for bone infection. In vitro-in vivo characterization

Abstract

To elucidate the antibiotic release mechanism from implants composed of calcium phosphates (hydroxyapatite [HAP] and tricalcium phosphate [TCP]), 30 kDa poly(DL-lactide) (PLA-30) and ciprofloxacin (CFX), nine formulations were prepared. In vitro results show that the release rate decreased as compression load and PLA/phosphates ratio increased. In contrast, a slower percent release rate was observed with higher drug loading. Swelling-erosion-disintegration of the implants was observed during the release assays, due to CFX swelling. Two CFX implant formulations were selected for implantation in the femur of rabbits, according to in vitro results. The implant drug loads tested were 10% and 40% of CFX. The in vivo results showed that the antibiotic concentrations achieved throughout the femur were higher for 4 weeks than the minimum inhibitory concentrations (MIC) against the most common of the pathogens that cause osteomyelitis. The CFX-10% implant was considered the best formulation as CFX was totally released within 6 weeks, and therapeutic bone levels were achieved, and the histological and radiographic analyses showed the osteoconductive properties of the materials. All these results showed that CFX release is limited by its solubility, and the erosion-disintegration and bone ingrowth into the implants enhanced the antibiotic release.