Abstract
Bone-like hydroxyapatite/poly amino acid (BHA/PAA) is a potential bone repair material. Rifapentine-loaded poly(lactic‑co‑glycolic acid) microspheres (RPMs) are bioactive and efficient controlled‑release delivery systems used invitro. The aim of the present study was to investigate the invivo drug release characteristics of RPM‑loaded BHA/PAA on a rabbit model of bone defect. RPM was combined with BHA/PAA to obtain the drug‑loaded, slow‑releasing bioactive material. Bone defects were generated in New Zealand white rabbits and the rabbits were then implanted with RPM‑loaded BHA/PAA. High‑performance liquid chromatography (HPLC) was used to determine the concentrations of rifapentine in the plasma and the local muscle tissues of the treated rabbits. Hematoxylin and eosin (H&E) staining and biochemical analyses were performed to elucidate potential side effects of RPM‑loaded BHA/PAA on the heart, liver and kidney histopathology and functions of the treated rabbits. The biocompatibility and osteogenic ability of RPM‑loaded BHA/PAA was evaluated by H&E staining. The results demonstrated that the material was completely degraded and absorbed at 12weeks following implantation and new trabecular bone and cartilage tissues had formed. The invivo release tests revealed that RPM‑loaded BHA/PAA exhibited sustained release profiles of rifapentine and the drug concentration in the muscle tissues remained higher than the minimum inhibitory concentration of rifapentine against Mycobacteriumtuberculosis for as long as 12weeks. In addition, RPM‑loaded BHA/PAA had no long‑term side effects to the heart, liver and kidney of the treated rabbits. In conclusion, the present study demonstrated that RPM‑loaded BHA/PAA slowly and continuously released rifapentine invivo and exhibited no side effects on heart, liver and kidney tissues and function. Furthermore, RPM‑loaded BHA/PAA promoted new bone formation, while it was gradually degraded and absorbed. The present study provided a theoretical basis for the potential advancement in developing novel treatments for osteoarticular tuberculosis.
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