Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, People's Republic of China.
Department of Pharmacy, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, People's Republic of China.
Int J Nanomedicine. 2024 Aug 6;19:7983-7996. doi: 10.2147/IJN.S462514. eCollection 2024.
Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.
Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.
In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.
In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.
骨质疏松症的特征是破骨细胞骨吸收和成骨细胞骨形成的失调，在衰老过程中严重威胁人类健康。然而，目前仍然没有治疗骨质疏松症的好方法，因此这一方向需要我们不断关注，迫切需要新的药物来解决这个问题。
传统中药丹参单体牡荆素（PA）能有效抑制破骨细胞分化和去卵巢骨质疏松症。然而，其较差的溶解度和缺乏靶向性严重限制了其进一步应用。本研究设计了一种新型骨靶向纳米药物（PA@TLipo），通过将牡荆素包裹在阿仑膦酸钠功能化的脂质体中，重建骨质疏松微环境。通过一系列操作，如合成、纯化、包封和标记，制备了 PA@TLipo。并通过细胞和动物实验验证了其细胞毒性、骨靶向性和抗骨质疏松作用。
在靶向方面，PA@TLipo 可以有效地聚集在骨组织上，减少骨丢失，在毒性方面，与非靶向脂质体相比，PA@TLipo 可以增加骨靶向能力，从而减轻全身细胞毒性。此外，PA@TLipo 抑制体外破骨细胞形成和骨吸收，减少去卵巢诱导的骨质疏松小鼠的骨丢失。
本研究设计并构建了一种新型治疗剂，用于治疗骨质疏松症，由脂质体材料作为药物口袋、PA 作为抗骨质疏松药物和 ALN 作为骨靶向分子组成。我们的研究首次采用骨靶向递药系统输送 PA 治疗 OVX 诱导的骨丢失，为治疗骨质疏松症提供了一种创新的解决方案。
