阿仑膦酸盐修饰的纳米颗粒作为骨靶向阿仑膦酸盐载体用于潜在的骨质疏松症治疗,ACS Applied Bio Materials

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阿仑膦酸盐修饰的纳米颗粒作为骨靶向阿仑膦酸盐载体用于潜在的骨质疏松症治疗
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2021-05-19 , DOI: 10.1021/acsabm.1c00199
Chunlan Jing ₁ , Bowen Li ₁ , Hui Tan ₂ , Chang Zhang ₁ , Hongze Liang ₁ , Haining Na ₃ , Shenmao Chen ₄ , Chaozong Liu ₄ , Lingling Zhao _{1,

2,

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Affiliation

骨质疏松症是一种以骨量和密度低为特征的骨骼疾病。第二代双膦酸盐药物阿仑膦酸盐（Alen）被指定为治疗骨质疏松症的一线方案。然而，由于其低生物利用度和胃肠道副作用，Alen 的使用受到限制。在此，通过聚（乳酸-共-乙醇酸）、β-环糊精改性壳聚糖（PLGA-CS-CD）和艾伦改性海藻酸盐（ALG-Alen）之间的离子交联制备了艾伦修饰的纳米粒子。装载和骨靶向递送。Alen 被选为治疗药物和骨靶向配体。纳米颗粒具有带负电荷的表面，并且可以观察到Alen从纳米颗粒中的持续释放。使用细胞计数试剂盒8（CCK-8）测定法检测细胞毒性，并对MC3T3细胞进行乳酸脱氢酶释放试验，结果表明纳米颗粒具有良好的细胞相容性。溶血试验表明纳米粒子的溶血率<5%，说明纳米粒子没有明显的溶血作用。此外，与没有 Alen 修饰的纳米粒子相比，Alen 修饰的纳米粒子对羟基磷灰石 (HAp) 盘的结合亲和力增强。因此，Alen 修饰的纳米颗粒可能被开发为有前途的骨靶向载体，用于治疗骨质疏松症。此外，与没有 Alen 修饰的纳米粒子相比，Alen 修饰的纳米粒子对羟基磷灰石 (HAp) 盘的结合亲和力增强。因此，Alen 修饰的纳米颗粒可能被开发为有前途的骨靶向载体，用于治疗骨质疏松症。此外，与没有 Alen 修饰的纳米粒子相比，Alen 修饰的纳米粒子对羟基磷灰石 (HAp) 盘的结合亲和力增强。因此，Alen 修饰的纳米颗粒可能被开发为有前途的骨靶向载体，用于治疗骨质疏松症。

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Alendronate-Decorated Nanoparticles as Bone-Targeted Alendronate Carriers for Potential Osteoporosis Treatment

Osteoporosis is a skeletal disorder characterized by a low bone mass and density. Alendronate (Alen), a second-generation bisphosphonate drug, was indicated as the first-line regimen for the treatment of osteoporosis. However, the use of Alen has been limited due to its low bioavailability and gastrointestinal side effects. Herein, Alen-decorated nanoparticles were prepared through ionic cross-linking between poly (lactic-co-glycolic acid), β-cyclodextrin-modified chitosan (PLGA-CS-CD), and Alen-modified alginate (ALG-Alen) for Alen loading and bone-targeted delivery. Alen was selected as a therapeutic drug and a bone-targeting ligand. The nanoparticles have negatively charged surfaces, and sustained release of Alen from the nanoparticles can be observed. Cytotoxicity detected using cell counting kit-8 (CCK-8) assay and lactate dehydrogenase release test on MC3T3 cells showed that the nanoparticles had good cytocompatibility. A hemolysis test showed that the hemolysis ratios of nanoparticles were <5%, indicating that the nanoparticles had no significant hemolysis effect. Moreover, the Alen-decorated nanoparticles exhibited enhanced binding affinity to the hydroxyapatite (HAp) disks compared with that of nanoparticles without Alen modification. Thus, the Alen-decorated nanoparticles might be developed as promising bone-targeted carriers for the treatment of osteoporosis.

更新日期：2021-06-21

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