ABSTRACT
Chronic osteomyelitis is still the cause of many problems in orthopaedics in terms of therapy and infection persistence. Four-to-six week systemic antibiotic therapy is required along with bone and soft tissue debridement in the therapy of chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken into consideration due to the side effects encountered in long-term high dose antibiotic use and the duration of hospitalization of the patients. Although local antibiotic therapy has been achieved by bone cement, a second surgical operation is needed for the removal of the system. On the other hand, heat generation during cement curing limits the use of heat-sensitive active ingredients. The most frequent osteomyelitis inducing micro-organism is gram (+) Staphylococcus aureus. In this study, teicoplanin, a glycopeptide antibiotic, active on gram (+) bacteria, was incorporated in a synthetic polymer in order to prepare a microsphere formulation for implantation to bone defects. Particle size, surface characteristics, loading capacity and in vitro release characteristics of the microspheres were determined as well as stability assessment of teicoplanin under accelerated conditions. In vivo studies were performed on rabbits and the microparticles were implanted intra-articularly to the lateral condylus of the femur. Antibiotic presence was detected by a microbiological assay from synovial fluid sample aspirated throughout 5 weeks. In the light of these evaluations, microspheres prepared from PLGA (75:25) (Mw 136,000) polymer were determined to be effective, and promising for obtaining prolonged local antibiotic release.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bone Diseases, Infectious/drug therapy , Microspheres , Teicoplanin/administration & dosage , Animals , Anti-Bacterial Agents/analysis , Biocompatible Materials , Biodegradation, Environmental , Delayed-Action Preparations , Drug Carriers , Drug Compounding/methods , Lactic Acid , Microbial Sensitivity Tests/methods , Microscopy, Electron, Scanning/methods , Osteomyelitis/complications , Particle Size , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Rabbits , Staphylococcal Infections/drug therapy , Synovial Fluid/metabolism , Teicoplanin/analysis , Time FactorsABSTRACT
Parenteral antibiotic therapy for acute bone infections, soft tissue infections and osteomyelitis may result in high serum concentrations, associated with nephrotoxic, ototoxic and allergic complications. After taking these above mentioned disadvantages into consideration, recent investigations have explored the use of antibiotic-loaded biodegradable implants, incorporating antibiotics for potential use in the treatment of bone infections. In this study, biodegradable implants containing teicoplanin for the prevention or the treatment of bone infections were designed by using sodium alginate as the polymer material. Therefore, teicoplanin, a glycopeptide antibiotic, active against gram-positive bacteria was incorporated in a natural polymer in order to prepare bead formulation for implantation purpose in bone for the localized treatment of osteomyelitis. In vitro characterization was realized by determining particle size, surface characteristics, loading capacity and in vitro release characteristics of the beads.
