Drug release of nano-hydroxyapatite biological substitute loaded with isoniazid and rifampin in vitro and animal models of spinal tuberculosis

Spinal tuberculosis drug efficacy studies have shown that a drug's clinical efficacy mainly depends on its concentration in the target tissue. To improve the local drug concentration of spinal tuberculosis, we studied the release of isoniazid and rifampin-loaded nano-hydroxyapatite biological substitutes in vitro and in animal models. In vitro experiments, isoniazid produced burst release, releasing 44.57% and 98.31% of drug at 24 h and four weeks, respectively. The rifampin release was relatively stable without obvious burst release. The release time of rifampin was longer, with 98.26% release in the 12 th week and the remaining 1.74% in biological substitute. In animal models, isoniazid concentration in biological substitutes of the vertebral body and paravertebral muscle gradually decreases and can be maintained until the 8 th week. The drug concentration in inferior vena cava reached its maximum at 72 h and then gradually decreased. No drug concentration was detected in the second week. The rifampin concentration in the vertebral body and parallel muscle reached the maximum in the first week, then decreased gradually and maintained to the 12 th and 8 th weeks. No drug concentration was detected in inferior vena cava after 72 h. Nano-hydroxyapatite biological substitute loaded with isoniazid and rifampin can be degraded stably in vitro and has good sustained-release properties. In animal models, antituberculosis drugs can be released continuously in the long term.