Yang Xinmin, Yang Xiaowei, Luo Peng, Zhong Yanlong, Zhang Bin, Zhu Weifeng, Liu Meiying, Zhang Xiaoyong, Lai Qi, Wei Yen
Department of Orthopedics, First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Zheng Street, Nanchang, Jiangxi, 330006, China.
Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang, 330031, China.
Mater Today Bio. 2023 Jun 3;20:100688. doi: 10.1016/j.mtbio.2023.100688. eCollection 2023 Jun.
Osteoporosis (OP) is a systemic metabolic orthopedic disorder prevalent in elderly people, that is characterized by a decrease in bone mass. Although many therapeutics have been adopted for OP treatment, many of them are still not well satisfied clinical requirements and therefore development of novel therapeutics is of great significance. In this work, a novel bone-targeting drug self-frame delivery system (DSFDS) with high drug loading efficiency and pH responsive drug release was fabricated by condensation of curcumin (Cur), amino group terminated polyethylene glycol (NH-PEG), and alendronate (ALN) using hexachlorocyclotriphosphonitrile (HCCP) as the linker. The final product named as HCCP-Cur-PEG-ALN (HCPA NPs) displayed excellent water dispersity with small size (181.9 ± 25.9 nm). Furthermore, the drug loading capacity of Cur can reach 25.8%, and Cur can be released from HCPA NPs under acidic environment. Owing to the introduction of ALN, HCPA NPs exhibited strong binding to HAp and excellent bone-targeting effect o. Results from cellular and biochemical analyses revealed that HCPA NPs could effectively inhibit the formation and differentiation function of osteoclasts. More importantly, we also demonstrated that HCPA NPs could effectively reduce bone loss in OVX mice with low toxicity to major organs. The above results clearly demonstrated that HCPA NPs are promising for OP treatment. Given the simplicity and well designability of fabrication strategy, explicit therapy efficacy and low toxicity of HCPA NPs, we believe that this work should be of great interest for fabrication of various DSFDS to deal with many diseases.
骨质疏松症（OP）是一种在老年人中普遍存在的全身性代谢性骨科疾病，其特征是骨量减少。尽管已经采用了许多治疗方法来治疗OP，但其中许多仍不能很好地满足临床需求，因此开发新型治疗方法具有重要意义。在这项工作中，以六氯环三磷腈（HCCP）为连接剂，通过姜黄素（Cur）、氨基封端的聚乙二醇（NH-PEG）和阿仑膦酸盐（ALN）缩合制备了一种具有高载药效率和pH响应性药物释放的新型骨靶向药物自组装递送系统（DSFDS）。最终产物命名为HCCP-Cur-PEG-ALN（HCPA纳米粒），具有优异的水分散性，粒径小（181.9 ± 25.9 nm）。此外，Cur的载药量可达25.8%，Cur可在酸性环境下从HCPA纳米粒中释放。由于引入了ALN，HCPA纳米粒与羟基磷灰石（HAp）表现出强结合力和优异的骨靶向效果。细胞和生化分析结果表明，HCPA纳米粒可有效抑制破骨细胞的形成和分化功能。更重要的是，我们还证明了HCPA纳米粒可以有效减少去卵巢（OVX）小鼠的骨质流失，对主要器官的毒性较低。上述结果清楚地表明，HCPA纳米粒在OP治疗方面具有潜力。鉴于制备策略的简单性和良好的可设计性、HCPA纳米粒明确的治疗效果和低毒性，我们相信这项工作对于制备各种用于治疗多种疾病的DSFDS具有重要意义。
