Gautam Namrata, Sharma Prashant, Chaudhary Antra, Sahu Surajita, Vohora Divya, Mishra Monalisa, Dutta Debopriya, Singh Manish, Talegaonkar Sushama
Department of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research University, New Delhi, India.
Institute of Nano Science and Technology (INST), Chemical Biology Unit, Mohali, India.
J Drug Target. 2025 May 16:1-16. doi: 10.1080/1061186X.2025.2503499.
Bisphosphonates and Hormone Replacement Therapy are the primary therapeutic interventions for Postmenopausal Osteoporosis (PMO), however, associated repercussions limit their usage. To address this challenge, we hypothesised the co-delivery of hydroxyapatite (HAP) with daidzein (DZ) for synergistic treatment of PMO. Propounding this bimodal approach, daidzein-loaded hydroxyapatite nanoparticles (DZHAPNPs) were prepared leveraging the oestrogenic properties of DZ while utilising HAP to facilitate biomineralization. The osteogenic potential of developed nanoparticles was validated through experiments on MG-63 cells and studies employing a "4-vinyl cyclohexene diepoxide-induced menopausal-mice model". DZHAPNPs exhibited pronounced pro-osteogenic activity, evidenced by enhanced (155.49%) alkaline phosphatase (ALP) activity in MG-63 cells. Additionally, cellular uptake studies confirmed their internalisation and targeted delivery. Following menopause induction and treatment, the mice underwent radiography, histology, micro-computed tomography (micro-CT) analysis, and biochemical evaluations. A significant reduction ( < 0.001) in biomarkers i.e., β-CTx, BALP, and TRAP-5b, post-treatment showed a substantial influence of DZ and DZHAPNPs. Better bone architectural parameters and bone mineral density in micro-CT analysis served as proof of the hypothesis. Also, the cellular biocompatibility of nanoparticles was confirmed through genotoxicity tests performed on the . The noteworthy results of the research substantiated the synergistic influence of DZ and HAPNPs in resilience and bone strength maintenance.
双膦酸盐和激素替代疗法是绝经后骨质疏松症（PMO）的主要治疗干预措施，然而，相关的不良反应限制了它们的使用。为应对这一挑战，我们假设将羟基磷灰石（HAP）与大豆苷元（DZ）共同递送用于PMO的协同治疗。提出这种双峰方法，利用DZ的雌激素特性制备了负载大豆苷元的羟基磷灰石纳米颗粒（DZHAPNPs），同时利用HAP促进生物矿化。通过对MG-63细胞的实验和采用“4-乙烯基环己烯二环氧化物诱导的绝经小鼠模型”的研究验证了所开发纳米颗粒的成骨潜力。DZHAPNPs表现出明显的促成骨活性，MG-63细胞中碱性磷酸酶（ALP）活性增强（155.49%）证明了这一点。此外，细胞摄取研究证实了它们的内化和靶向递送。在诱导绝经和治疗后，对小鼠进行了放射照相、组织学、显微计算机断层扫描（micro-CT）分析和生化评估。治疗后生物标志物即β-CTx、BALP和TRAP-5b的显著降低（<0.001）表明DZ和DZHAPNPs有重大影响。micro-CT分析中更好的骨结构参数和骨密度证明了这一假设。此外，通过对……进行的遗传毒性测试证实了纳米颗粒的细胞生物相容性。该研究的显著结果证实了DZ和HAPNPs在恢复力和维持骨强度方面的协同影响。
