Chronic osteomyelitis is a chronic infection of bone and its marrow. It is commonly associated with some diseases like sickle cells disease, diabetes, and arthritis. Chronic osteomyelitis treatment is complex, due to the difficulty to achieve therapeutic drug levels at the site of infection by systemic administration.
Our objective was to develop a biodegradable implant based on gentamicin and monoolein. It should be able to make a sustained release of the gentamicin in the site of infection. This novel formulation should be biocompatible and efficacious to treat chronic osteomyelitis.
Four formulations of implants based on gentamicin and monoolein were made. The final products were homogenous gels, becoming more solid in contact with water. Hot stage microscopy, DSC, thermogravimetric analysis (TGA), X-ray diffraction, and determination of moisture contents (Karl Fischer titration) showed cubic liquid crystalline and eutectic structures of the implants. Only the formulation consisting of 80-15-5% w/w monoolein- water-gentamicin sulfate progressively released the totality of the antibiotic for a period of twenty days without burst effect. This formulation was selected for the following studies. The implants were physically instable at room temperature by stable when they were kept cool (2- 6 °C) during at least 10 months. Their in vitro drug release characteristics were not changed in the same conditions (after storage for 10 months at 2 – 6 ° C).
The Lysat d’amoebocyte de Limule (LAL) and sterility assays proved that the implants were made according to the Good Laboratory Practice. They were sterile and apyrogen.
The MTT and comet assays performed with fibroblasts and macrophages revealed that the implants were non-cytotoxic and were not potentially genotoxic. They were also compatible in vitro with blood erythrocytes.
The biocompatibility and toxicity of the implants assessed in vivo revealed that they were well tolerated and had acceptable biocompatibility at long-term.
As for clinical assessment of the implants, 19 patients with chronic osteomyelitis caused by a microorganism sensitive to gentamicin were included. After surgical curettage of the infected bone, the dead space was filled in with the implants. To prevent post-operative septicaemia, a systemic antibiotherapy was prescribed for 3 days following the operation.
Clinical, biological and radiological follow-up (range from 2 to 12 months) revealed that 18
patients recovered from chronic osteomyelitis (within 30-70 days) without adverse events.
The wound of one patient whose bone was exposed did not scar over after 10 months.
However, it was no longer infected.
Further investigations through randomized multicentric trials will be done in order to obtain trade license.