Snega Priya P, Surisetti Rachitha, Gopi Sanjay, Pachaiappan Raman, Pasupuleti Mukesh, Rajagopal Rajakrishnan, Alfarhan Ahmed, Guru Ajay, Arockiaraj Jesu
Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulatur 603203, Chengalpattu District, Tamil Nadu, India.
Department of Biotechnology, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India.
Int J Biol Macromol. 2024 Sep 14;280(Pt 1):135662. doi: 10.1016/j.ijbiomac.2024.135662.
The use of nanotechnology and polymer-based carriers in osteoporosis treatment offers promising avenues for targeted drug delivery and enhanced therapeutic efficacy. In this study, we developed a novel nanoconjugate composed of Chitosan (CH), Chondroitin Sulfate (CS), and Daidzein (DZ) to treat glucocorticoid-induced osteoporosis in an in vivo zebrafish model. The CH-CS-DZ nanoconjugate were synthesized using the ionic gelation method, with a CH: CS ratio of 1:1 and a 3 % DZ concentration was identified as optimal for further analysis. The resulting nanoparticles exhibited a particle size of 401.2 ± 0.87 nm. The polydispersity index (PDI) and zeta potential of nanoconjugate were of 0.147 ± 0.04 and 43.55 ± 0.68 mV respectively. Drug release studies demonstrated that 79.66 ± 4.04 % of DZ was released under physiological conditions (pH 7.5) after 96 h, indicating a sustained release profile beneficial for prolonged therapeutic effects. In vivo, studies using zebrafish larvae revealed a significant reduction in oxidative stress and apoptosis in the CH-CS-DZ treated group compared to the glucorticoid dexamethasone (Dex) treated group. Specifically, reactive oxygen species (ROS) levels were reduced, and lipid peroxidation was markedly decreased (p < 0.001) in the CH-CS-DZ treated group. Additionally, the survival and hatching rates of CH-CS-DZ-treated larvae were 94 % and 95 %, respectively, significantly higher than those in the Dex-treated group. The CH-CS-DZ nanoconjugate also restored bone mineralization, as evidenced by a significant increase in calcium deposition (p < 0.001) and alkaline phosphatase (ALP) activity (122 ± 0.4 U/L), compared to the Dex group (84 ± 0.7 U/L). Gene expression analysis showed upregulation of OPG and ALP and downregulation of RANKL and RUNX2b, further indicating the anti-osteoporotic potential of the CH-CS-DZ nanoconjugates. These findings suggest that polymer-based nanoconjugates like CH-CS-DZ can effectively mitigate osteoporosis through targeted delivery and sustained release, offering a potent strategy for bone health restoration.
在骨质疏松症治疗中使用纳米技术和基于聚合物的载体为靶向给药和提高治疗效果提供了有前景的途径。在本研究中，我们开发了一种由壳聚糖（CH）、硫酸软骨素（CS）和大豆苷元（DZ）组成的新型纳米缀合物，用于在体内斑马鱼模型中治疗糖皮质激素诱导的骨质疏松症。采用离子凝胶法合成了CH-CS-DZ纳米缀合物，确定CH:CS比例为1:1且DZ浓度为3%为进一步分析的最佳条件。所得纳米颗粒的粒径为401.2±0.87nm。纳米缀合物的多分散指数（PDI）和zeta电位分别为0.147±0.04和43.55±0.68mV。药物释放研究表明，96小时后在生理条件（pH 7.5）下79.66±4.04%的DZ被释放，表明其具有持续释放特性，有利于延长治疗效果。在体内，使用斑马鱼幼虫的研究显示，与糖皮质激素地塞米松（Dex）治疗组相比，CH-CS-DZ治疗组的氧化应激和细胞凋亡显著降低。具体而言，CH-CS-DZ治疗组的活性氧（ROS）水平降低，脂质过氧化显著减少（p<0.001）。此外，CH-CS-DZ处理的幼虫的存活率和孵化率分别为94%和95%，显著高于Dex处理组。与Dex组（84±0.7U/L）相比，CH-CS-DZ纳米缀合物还恢复了骨矿化，钙沉积（p<0.001）和碱性磷酸酶（ALP）活性（122±0.4U/L）显著增加证明了这一点。基因表达分析显示OPG和ALP上调，RANKL和RUNX2b下调，进一步表明CH-CS-DZ纳米缀合物的抗骨质疏松潜力。这些发现表明，像CH-CS-DZ这样的基于聚合物的纳米缀合物可以通过靶向递送和持续释放有效减轻骨质疏松症，为恢复骨骼健康提供了一种有效的策略。
