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透明质酸修饰的利塞膦酸钠和特立帕肽共载纳米载体促进成骨细胞成骨分化用于骨质疏松症的治疗。

Hyaluronic Acid Modified Risedronate and Teriparatide Co-loaded Nanocarriers for Improved Osteogenic Differentiation of Osteoblasts for the Treatment of Osteoporosis.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.

Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.

出版信息

Curr Pharm Des. 2019;25(27):2975-2988. doi: 10.2174/1381612825666190801140703.

DOI:10.2174/1381612825666190801140703
PMID:31368869
Abstract

BACKGROUND

Owing to its multifactorial intricate pathogenesis, combined therapeutic regimen is considered appropriate for the treatment of osteoporosis. However, a multi-drug regimen is also associated with adverse effects due to the non-specific distribution of drugs. Therefore, the present study aims for efficient codelivery of risedronate (RDN) (a potent bone anti-resorptive drug) and teriparatide (TPD) (anabolic agent) as hyaluronic acid (HA)-modified chitosan nanoparticles (NPs).

METHODS

RDN/TPD NPs were synthesized using the high- pressure homogenization - solvent evaporation technique. The fabricated NPs were then characterized and optimized for suitable physicochemical characteristics. The optimized NPs were then evaluated for bone remodeling potential via assessment of time-mannered modulation in proliferation, differentiation, and mineralization of osteoblasts.

RESULTS

Results showed that HA-RDN/TPD NPs exhibited excellent physicochemical characteristics (nanoscopic size, stable zeta potential, high entrapment efficiency, and smooth spherical shape) and remained stable upon storage in the refrigerator. Assessment of various aspects of the cell growth cycle (i.e., proliferation, differentiation, and mineralization) evidenced promising bone regeneration efficacy of HA-RDN/TPD NPs.

CONCLUSION

This new strategy of employing simultaneous delivery of anti-resorptive and bone-forming agents would open new horizons for scientists, researchers, and healthcare providers as an efficient pharmacotherapy for the treatment of osteoporosis.

摘要

背景

由于其多因素复杂的发病机制,联合治疗方案被认为是骨质疏松症治疗的合适选择。然而,由于药物的非特异性分布,多药物治疗方案也会引起不良反应。因此,本研究旨在通过将利塞膦酸钠(RDN)(一种有效的骨抗吸收药物)和特立帕肽(TPD)(一种合成代谢药物)作为透明质酸(HA)修饰壳聚糖纳米颗粒(NPs)进行有效的共递送来解决这个问题。

方法

使用高压匀质-溶剂蒸发技术合成 RDN/TPD NPs。然后对所制备的 NPs 进行表征和优化,以获得合适的物理化学特性。然后通过评估成骨细胞增殖、分化和矿化的时间方式调节来评估优化后的 NPs 对骨重塑潜力的影响。

结果

结果表明,HA-RDN/TPD NPs 表现出优异的物理化学特性(纳米级尺寸、稳定的 ζ 电位、高包封效率和光滑的球形形状),并且在冰箱中储存时仍然稳定。对细胞生长周期的各个方面(即增殖、分化和矿化)的评估表明,HA-RDN/TPD NPs 具有有前途的骨再生功效。

结论

这种同时递送抗吸收和骨形成剂的新策略为科学家、研究人员和医疗保健提供者提供了一个新的视野,作为骨质疏松症治疗的有效药物治疗策略。

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