Wang Zhen, Song Xinghua, Yang Huan, Maimaitiaili Abulikemu, Wang Tengfei
Department of Orthopeadics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Department of Orthopeadics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China; Department of Orthopeadics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Ann Palliat Med. 2020 Mar;9(2):375-387. doi: 10.21037/apm.2020.03.13. Epub 2020 Mar 17.
This study aimed to develop and evaluate a sustained drug delivery system for the treatment of osteoarticular tuberculosis (TB) to address the issues surrounding low drug concentration in lesions and bone defects or nonunion after debridement.
The effects of rifapentine on the proliferation and cell cycle of bone marrow mesenchymal stem cells (BMSCs) were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Rifapentine polylactic acid (PLA) sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method and investigated the antibacterial activity in vitro. In this study, two sustained drug delivery systems were prepared by integrating RPSMs and BMSCs into hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) or allogeneic bone. We evaluated these drug delivery systems for dynamics of drug release and osteogenic ability by in vitro release test, alkaline phosphatase (ALP) and alizarin red staining, and real-time PCR.
The results showed that rifapentine concentrations up to 45.0 μg/mL had no effect on cell proliferation and cell cycle. The encapsulation and drug loading efficiency of the fabricated RPSMs were 78.11%±1.16% and 35.57%±0.85%, respectively. The RPSMs had uniform particle size distribution and a long-term anti-bacterium effect. The HA/β-TCP-implanted drug delivery system was found to be more effective in reducing the burst release and having a longer duration of sustained release and retention compared to allogeneic bone. The ALP and alizarin red staining and real-time PCR results showed that it had excellent osteoconductive and osteoinductive properties.
In conclusion, the sustained drug delivery system with HA/β-TCP as scaffold material represents a potential new strategy for TB infections and bone defects.
本研究旨在开发和评估一种用于治疗骨关节结核的持续给药系统，以解决病灶内药物浓度低以及清创术后骨缺损或骨不连等问题。
采用细胞计数试剂盒-8（CCK-8）和流式细胞术评估利福喷汀对骨髓间充质干细胞（BMSC）增殖和细胞周期的影响。通过复乳溶剂蒸发法制备利福喷汀聚乳酸（PLA）缓释微球（RPSM），并研究其体外抗菌活性。在本研究中，通过将RPSM和BMSC整合到羟基磷灰石/β-磷酸三钙（HA/β-TCP）或同种异体骨中，制备了两种持续给药系统。我们通过体外释放试验、碱性磷酸酶（ALP）和茜素红染色以及实时聚合酶链反应评估了这些给药系统的药物释放动力学和成骨能力。
结果表明，高达45.0μg/mL的利福喷汀浓度对细胞增殖和细胞周期无影响。制备的RPSM的包封率和载药效率分别为78.11%±1.16%和35.57%±0.85%。RPSM具有均匀的粒径分布和长期抗菌效果。与同种异体骨相比，发现植入HA/β-TCP的给药系统在减少突释、具有更长的持续释放和保留时间方面更有效。ALP和茜素红染色以及实时聚合酶链反应结果表明，它具有优异的骨传导性和骨诱导性。
总之，以HA/β-TCP为支架材料的持续给药系统代表了一种治疗结核感染和骨缺损的潜在新策略。
