Rasoulian Bita, Poormoghadam Delaram, Hoveizi Elham, Rezayat Seyed Mahdi, Tavakol Shima
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
School of biomedical Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Nanoscale. 2025 Jan 23;17(4):2091-2104. doi: 10.1039/d4nr02884h.
The burgeoning field of nano-bone regeneration is yet to establish a definitive optimal particle size for nanocarriers. This study investigated the impacts of nanocarrier's particle size on the bone regeneration efficacy of fingolimod (FTY720)-loaded nanoemulsions. Two distinct particle sizes (60 and 190 nm, designated as NF60 and NF190, respectively) were produced using low-energy and high-energy emulsion techniques, maintaining a consistent surfactant, co-surfactant, and oil. studies using rat mesenchymal stem cells revealed that both NF60 and NF190 exhibited cell viability and reduced lactate dehydrogenase. Interestingly, NF60 demonstrated superior antioxidant properties, significantly reducing nitric oxide and intracellular reactive oxygen species (ROS) levels compared to NF190. Furthermore, NF60 significantly enhanced ALP activity and calcium deposition during osteogenic differentiation, indicating its potential to promote the early stages of bone formation. studies using a rat calvarial bone defect model demonstrated that both NF60 and NF190 significantly upregulated the expression of key osteogenic genes, including Runx2, Col, ALP, OCN, and BMP2. Notably, NF60 induced significantly higher expression of Runx2 and BMP2. X-ray and histological investigations revealed significantly improved bone regeneration in the NF60 group, highlighting the superior bone healing potential of smaller FTY720 nanoemulsions, without infiltration of inflammatory cells. The smaller particle size demonstrated superior antioxidant properties, enhanced osteogenic differentiation, and improved bone regeneration, suggesting smaller nanoparticles, with their larger surface area, accelerated drug release rate, and lower viscosity, interact more effectively with cells, leading to increased and effective drug delivery and cellular uptake. Findings highlight the importance of nanocarrier size in optimizing drug delivery for bone tissue engineering applications.
纳米骨再生这一新兴领域尚未确定纳米载体的最佳粒径。本研究调查了纳米载体粒径对负载芬戈莫德（FTY720）的纳米乳剂骨再生效果的影响。使用低能和高能乳化技术制备了两种不同的粒径（60和190纳米，分别指定为NF60和NF190），同时保持表面活性剂、助表面活性剂和油的一致性。使用大鼠间充质干细胞的研究表明，NF60和NF190均表现出细胞活力并降低了乳酸脱氢酶水平。有趣的是，与NF190相比，NF60表现出更强的抗氧化性能，显著降低了一氧化氮和细胞内活性氧（ROS）水平。此外，NF60在成骨分化过程中显著增强了碱性磷酸酶活性和钙沉积，表明其具有促进骨形成早期阶段的潜力。使用大鼠颅骨缺损模型的研究表明，NF60和NF190均显著上调了关键成骨基因（包括Runx2、Col、ALP、OCN和BMP2）的表达。值得注意的是，NF60诱导Runx2和BMP2的表达显著更高。X射线和组织学研究显示，NF60组的骨再生显著改善，突出了较小的FTY720纳米乳剂具有更好的骨愈合潜力，且无炎性细胞浸润。较小的粒径表现出更强的抗氧化性能、增强的成骨分化和改善的骨再生，表明较小的纳米颗粒因其更大的表面积、更快的药物释放速率和更低的粘度，能更有效地与细胞相互作用，从而提高药物递送和细胞摄取的效率。研究结果突出了纳米载体尺寸在优化骨组织工程应用药物递送方面的重要性。
