An efficient treatment for osteoarthritis (OA) can benefit from the local release of a high therapeutic dose over an extended period of time. Such a treatment will minimize systemic side effects and avoid the inconvenience of frequent injections. To this aim, nanocrystal–polymer particles (NPPs) are developed by combining the advantages of nanotechnology and microparticles. Nanocrystals are produced by wet milling kartogenin (KGN), which is known to promote chondrogenesis and to foster chondroprotection. A fluorescent biodegradable polymer is synthesized for intravital particle tracking. Polymer microparticles with 320 nm embedded KGN nanocrystals (KGN‐NPPs) show a high drug loading of 31.5% (w/w) and an extended drug release of 62% over 3 months. In vitro, these particles do not alter mitochondrial activity in cultured human OA synoviocytes. In vivo, KGN‐NPPs demonstrate higher bioactivity than a KGN solution in a murine mechanistic OA model based on histological assessment (Osteoarthritis Research Society International score), epiphyseal thickness (microcomputed tomography), OA biomarkers (e.g., vascular endothelial growth factor, Adamts5), and prolonged intra‐articular persistence (fluorescence analysis). This work provides proof‐of‐concept of a novel and innovative extended drug delivery system with the potential to treat human OA.

中文翻译：

---

纳米晶体-聚合物颗粒：骨关节炎治疗的扩展载体

骨关节炎（OA）的有效治疗可以受益于长期释放的高治疗剂量。这种治疗将使全身性副作用减至最小，并避免频繁注射的不便。为此，结合了纳米技术和微粒的优点，开发出了纳米晶体-聚合物微粒（NPP）。纳米晶体是通过湿磨卡托金菌素（KGN）来生产的，已知它可以促进软骨形成和促进软骨保护作用。合成荧光可生物降解的聚合物用于体内颗粒追踪。具有320 nm嵌入KGN纳米晶体（KGN-NPPs）的聚合物微粒在3个月内显示出31.5％（w / w）的高载药量和62％的延长药物释放。在体外，这些颗粒不会改变培养的人OA滑膜细胞中的线粒体活性。在体内，根据组织学评估（骨关节炎研究协会国际评分），骨s厚度（微计算机断层扫描），OA生物标志物（例如，血管内皮生长因子，Adamts5），在小鼠机械性OA模型中，KGN-NPPs的生物活性高于KGN解决方案。 ，并延长关节内持续性（荧光分析）。这项工作提供了一种新颖的，创新的，扩展的药物输送系统的概念验证，该系统具有治疗人类OA的潜力。并延长了关节腔内的持久性（荧光分析）。这项工作提供了一种新颖的，创新的，扩展的药物输送系统的概念验证，该系统具有治疗人类OA的潜力。并延长了关节腔内的持久性（荧光分析）。这项工作提供了一种新颖的，创新的，扩展的药物输送系统的概念验证，该系统具有治疗人类OA的潜力。