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Research Article

HSIM负载聚合物纳米粒子的分子复合物：骨质疏松症的潜在载体

卷 24, 期 13, 2023

发表于: 22 September, 2023

页: [1066 - 1078] 页: 13

弟呕挨: 10.2174/1389450124666230915092910

价格: $65

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摘要

背景：他汀类药物，尤其是辛伐他汀，通过BMP-Smad信号通路刺激成骨细胞活性和抑制破骨细胞活性，从而促进骨形成。他汀类药物呈现肝脏先过代谢。本研究试图制备和评估包埋在具有缓释特性的聚乳酸-羟基乙酸（PLGA）纳米颗粒（HSIM-PLGA NPs）中的辛伐他汀功能化羟基磷灰石，用于有效治疗骨质疏松症。 方法：通过搅拌制备辛伐他汀功能化羟基磷灰石（HSIM），并通过对接研究、傅立叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）和X射线衍射（XRD）进行验证。此外，通过溶剂乳化法开发了负载HSIM的PLGA纳米颗粒（HSIM-PLGA NPs）。对纳米颗粒的ζ电位、粒径、包封效率、稳定性研究和体外药物释放研究进行了评估。还测定了纳米粒子与羟基磷灰石的体外结合亲和力。采用糖皮质激素诱导的骨质疏松大鼠模型，观察骨形态及其对骨密度的影响。 结果：优化后的纳米颗粒是无定形的，没有药物-聚合物相互作用。配制的纳米颗粒的粒径从196.8±2.27nm变化到524.8±5.49nm，纳米颗粒的包封率分别从41.9±3.44%变化到70.8±4.46%。纳米颗粒显示出药物的持续释放行为（24小时内75%），然后是非斐济药物释放。纳米颗粒表现出对骨细胞受体的高结合亲和力，增加了骨矿物质密度。在疾病和治疗大鼠中观察到钙和磷水平的显著差异。在骨质疏松大鼠和治疗大鼠中分别观察到多孔骨和孔隙率的显著改善（p<0.05）。 结论：掺入功能化辛伐他汀的骨靶向纳米颗粒可以靶向骨。因此，为了将辛伐他汀皮下分配用于治疗骨质疏松症，所开发的纳米颗粒可能是一种有前途的方法。

关键词: 羟基磷灰石，辛伐他汀，靶向，纳米颗粒，聚乳酸-羟基乙酸，缓释。

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