The slow release performance of calcium sulfate/poly(amino acid) compound materials carrying triple anti-tuberculosis drugs in a rabbit model of spinal tuberculosis / 中国组织工程研究

ABSTRACT

BACKGROUND: Calcium sulfate/poly amino acid compound materials carrying triple anti-tuberculosis drugs have been proved to have excellent slow release performance based on our preliminary studies on the physical and chemical properties and the release properties of the compound materials.OBJECTIVE: To observe the slow release performance of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs in a rabbit model of spinal tuberculosis.METHODS: Twenty-four New Zealand white rabbits were used to make L4-5 spinal tuberculosis models and divided into two groups in a random way following removal of tuberculosis lesions. Calcium sulfate/poly amino acid compound material carrying isoniazide, rifampicin, pyrazinamide or calcium sulfate/poly(amino acid)compound material with no drugs was implanted into the defect in the experimental or control group,respectively. At 2, 4, 6 and 8 weeks after implantation, the concentrations of isoniazid, rifampicin and pyrazinamide in the defect region, including the bone tissue, adjacent psoas major and inferior vena cava,were measured.RESULTS AND CONCLUSION: In the experimental group, the isoniazid levels in the damaged bone tissue and psoas major were kept in minimum bactericidal concentration (MBC) at 8 weeks after implantation and in the minimum inhibitory concentration (MIC) at the end of 12 weeks after implantation, while its level in the vein was kept in MBC at 2 weeks and in MIC at 8 weeks. The rifampicin levels in the bone tissue and psoas major were kept in MBC at 4 weeks after implantation and in the MIC at 8 weeks after implantation, while its level in the vein was kept MIC at 4 weeks.The pyrazinamide levels in the damaged bone tissue and psoas major were kept in MBC at 8 weeks after implantation and in the MIC until 8 weeks after implantation, while its level in the vein was kept MIC at 8 weeks. In the control group,there were no levels of isoniazid, rifampicin and pyrazinamide in the damaged bone tissue, adjacent psoas major and inferior vena cava in comparison with the baseline. These results show that isoniazid, rifampicin and pyrazinamide in the defect region can achieve sustained slow release in the rabbit model of spinal tuberculosis after implantation of the calcium sulfate/poly(amino acid) compound material carrying triple anti-tuberculosis drugs. In addition, the local drug concentration and duration in the defect region are better than those in the blood.