An in vitro study of composites of poly(L-lactide-co-ε-caprolactone), ß-tricalcium phosphate and ciprofloxacin intended for local treatment of osteomyelitis.

Osteomyelitis is a bacterial disease that can become chronic, and treatment often includes a surgical operation to remove infected bone. The aim of this study was to develop and investigate in vitro bone filling composite materials that release ciprofloxacin to kill any remaining bacteria and contain bioceramic to help the bone to heal. Three composites of poly(L-lactide-co-ε-caprolactone), ß-tricalcium phosphate and ciprofloxacin were compounded using twin-screw extrusion and sterilized by gamma irradiation. Drug release and degradation of the composites were investigated in vitro for 52 weeks. The composite with 50 wt% of ß-TCP had the most promising ciprofloxacin release profile. The ceramic component accelerated the drug release that occurred in three phases obeying first-order kinetics. Inhibition zone testing using bioluminescence showed that the released ciprofloxacin had effect in eradicating a common osteomyelitis causing bacteria Pseudomonas aeruginosa. During the in vitro degradation test series, molar weight of the polymer matrix of the composites decreased rapidly. Additionally, (1)H-NMR analysis showed that the polymer had blocky structure and the comonomer ratio changed during hydrolysis. The tested composites showed great potential to be developed into bone filler materials for the treatment of osteomyelitis or other bone related infections.

Processing and sustained in vitro release of rifampicin containing composites to enhance the treatment of osteomyelitis.

The objective in this study was to develop an osteoconductive, biodegradable and rifampicin releasing bone filling composite material for the treatment of osteomyelitis, a bacterial infection of bone that is very difficult and expensive to treat. The composite material will be used together with a ciprofloxacin releasing composite, because of the rapid development of resistant bacteria when rifampicin is used alone. Three composites were manufactured by twin-screw extrusion. The polymer matrix for the composites was poly(L-lactide-co-ε-caprolactone) 70/30 and all the composites contained 8 wt% (weight percent) of rifampicin antibiotic. The ß-TCP contents of the composites were 0 wt%, 50 wt% and 60 wt%. The composites were sterilized by gamma irradiation before in vitro degradation and drug release tests. The hydrolytical degradation of the studied composites proceeded quickly and the molecular weight of the polymer component of the composites decreased rapidly. Rifampicin release occurred in four phases in which the high ß-TCP content of the samples, polymer degradation and mass loss all played a role in determining the phases. The ceramic component was seen to have a positive effect on the drug release. The composite with 50 wt% of ß-TCP showed the most promising rifampicin release profile and it also showed activity against a common osteomyelitis causing bacteria Pseudomonas aeruginosa. A clear inhibition zone was formed in 16 h incubation. Overall, the tested materials showed great potential to be developed into a bone filler material for the treatment of osteomyelitis or other bone related infections in combination with the ciprofloxacin releasing materials.