Tianjin Medical University, Tianjin, China; Department of Spinal Surgery, Tianjin Union Medical Center, Tianjin, China.
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
Int J Pharm. 2024 Aug 15;661:124457. doi: 10.1016/j.ijpharm.2024.124457. Epub 2024 Jul 9.
Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.
骨质疏松症是一种常见的系统性骨代谢疾病，主要影响绝经后妇女，其特征是骨脆性增加和骨折风险升高。目前骨质疏松症治疗的疗效往往受到非特异性药物靶向和不理想的非靶骨骼副作用的限制。为了解决这一挑战，我们开发了一种新型的羟基磷灰石响应性药物传递系统。该系统利用自组装的对-膦酸酯杯[4]芳烃四癸基醚（PC4A12C），专门针对骨重塑部位的骨质疏松症药物进行靶向并持续释放。我们的重点是淫羊藿苷（ICA），一种以其强大的成骨特性和最小的不良反应而闻名的药物。在体外，载有 ICA 的 PC4A12C（ICA@PC4A12C）在骨髓间充质干细胞（BMSCs）中表现出增强的增殖、分化和矿化。在体内，ICA@PC4A12C 表现出对骨组织的优异靶向效果，确保 ICA 能够在骨环境中得到控制和缓慢释放。在骨质疏松症小鼠模型中，与单独使用 ICA 相比，用 ICA@PC4A12C 治疗显示出明显增强的成骨活性和显著增加的骨密度。这些结果表明 PC4A12C 作为一种有效的药物载体，在开发先进的抗骨质疏松药物传递系统方面具有潜力。
