Sun Xiaoduan, Lin Yan, Zhong Xingyue, Fan Chao, Liu Zhen, Chen Xin, Luo Zaiyi, Wu Jili, Tima Singkome, Zhang Zhirong, Jiang Jun, Du Xingjie, Zhou Xiangyu, Zhong Zhirong
Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China.
Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
J Control Release. 2024 Dec;376:37-51. doi: 10.1016/j.jconrel.2024.10.002. Epub 2024 Oct 9.
Formulating drugs into nanoparticles that target sites of disease can lead to strong therapeutic effects with lower doses of drugs and lower rates of off-target adverse effects. Few ways to target drugs to bone have been described, hampering the treatment of osteoporosis. Here we exploit the ability of alendronate to bind tightly to hydroxyapatite in bone as a tactic to target polymeric micelles loaded with the plant flavonoid icaritin to osteoporotic lesions. The traditional Chinese medicine icaritin, from Herba Epimedii, has previously been shown to inhibit adipogenesis and enhance osteogenesis by bone mesenchymal stem cells, but the compound on its own persists only briefly in the bloodstream. Our delivery system led to stronger inhibition of adipogenesis and activation of osteogenesis in a rat model of osteoporosis than when the icaritin-loaded micelles lacked alendronate. These results establish the feasibility of using alendronate to target osteogenic phytomolecules to sites of bone injury, which may guide the development of effective therapies against osteoporosis and, by extension, other bone disorders.
将药物制成靶向疾病部位的纳米颗粒，可以用较低剂量的药物产生强大的治疗效果，并降低脱靶不良反应的发生率。目前针对骨骼靶向给药的方法很少，这阻碍了骨质疏松症的治疗。在此，我们利用阿仑膦酸盐与骨中羟基磷灰石紧密结合的能力，将负载植物黄酮类化合物淫羊藿素的聚合物胶束靶向到骨质疏松性病变部位。传统中药淫羊藿素此前已被证明可抑制脂肪生成并增强骨髓间充质干细胞的成骨作用，但该化合物单独存在时在血液中仅短暂存留。与不含阿仑膦酸盐的负载淫羊藿素的胶束相比，我们的递送系统在骨质疏松大鼠模型中对脂肪生成的抑制作用更强，对成骨的激活作用也更强。这些结果证实了利用阿仑膦酸盐将成骨植物分子靶向到骨损伤部位的可行性，这可能会为抗骨质疏松症以及其他骨疾病的有效治疗方法的开发提供指导。
