Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1425-1430. doi: 10.3892/mmr.2017.6747. Epub 2017 Jun 9.
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 in vitro. The aim of the present study was to investigate the in vivo 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 12 weeks following implantation and new trabecular bone and cartilage tissues had formed. The in vivo 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 Mycobacterium tuberculosis for as long as 12 weeks. 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 in vivo 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.
骨样羟基磷灰石/聚氨基酸（BHA/PAA）是一种有潜力的骨修复材料。利福喷丁载聚乳酸-共-羟基乙酸（PLGA）微球（RPM）是一种生物活性和高效的控释给药系统，已在体外得到应用。本研究旨在研究 RPM 载 BHA/PAA 在兔骨缺损模型中的体内药物释放特性。将 RPM 与 BHA/PAA 结合，获得载药、缓释的生物活性材料。在新西兰白兔中制备骨缺损模型，并植入 RPM 载 BHA/PAA。采用高效液相色谱法（HPLC）测定血浆和处理兔局部肌肉组织中利福喷丁的浓度。采用苏木精-伊红（H&E）染色和生化分析方法，阐明 RPM 载 BHA/PAA 对心脏、肝脏和肾脏组织病理学和功能的潜在副作用。采用 H&E 染色评价 RPM 载 BHA/PAA 的生物相容性和成骨能力。结果表明，植入后 12 周，材料完全降解和吸收，形成新的小梁骨和软骨组织。体内释放试验表明，RPM 载 BHA/PAA 对利福喷丁具有持续释放特性，药物在肌肉组织中的浓度在 12 周内始终高于利福喷丁对结核分枝杆菌的最低抑菌浓度。此外，RPM 载 BHA/PAA 对处理兔的心脏、肝脏和肾脏无长期副作用。综上所述，本研究表明，RPM 载 BHA/PAA 可在体内缓慢、持续地释放利福喷丁，对心脏、肝脏和肾脏组织及功能无副作用。此外，RPM 载 BHA/PAA 促进新骨形成，同时逐渐降解和吸收。本研究为开发治疗骨关节结核的新型治疗方法提供了理论依据。
