宣少燕, 朱月, 张林, 唐志华, 徐锋, 陈滕, 汪祖华. 透明质酸温敏水凝胶介导的重组人甲状旁腺激素(1-34)可控释放与细胞生物学研究J. 药学学报, 2022,57(3): 809-817. doi: 10.16438/j.0513-4870.2021-0999
引用本文: 宣少燕, 朱月, 张林, 唐志华, 徐锋, 陈滕, 汪祖华. 透明质酸温敏水凝胶介导的重组人甲状旁腺激素(1-34)可控释放与细胞生物学研究J. 药学学报, 2022,57(3): 809-817. doi: 10.16438/j.0513-4870.2021-0999
XUAN Shao-yan, ZHU Yue, ZHANG Lin, TANG Zhi-hua, XU Feng, CHEN Teng, WANG Zu-hua. Controlled release and cytobiology of recombinant human parathyroid hormone 1-34 mediated by hyaluronic acid thermo-sensitive hydrogelsJ. Acta Pharmaceutica Sinica, 2022,57(3): 809-817. doi: 10.16438/j.0513-4870.2021-0999
Citation: XUAN Shao-yan, ZHU Yue, ZHANG Lin, TANG Zhi-hua, XU Feng, CHEN Teng, WANG Zu-hua. Controlled release and cytobiology of recombinant human parathyroid hormone 1-34 mediated by hyaluronic acid thermo-sensitive hydrogelsJ. Acta Pharmaceutica Sinica, 2022,57(3): 809-817. doi: 10.16438/j.0513-4870.2021-0999

透明质酸温敏水凝胶介导的重组人甲状旁腺激素(1-34)可控释放与细胞生物学研究

Controlled release and cytobiology of recombinant human parathyroid hormone 1-34 mediated by hyaluronic acid thermo-sensitive hydrogels

  • 摘要: 促成骨剂重组人甲状旁腺激素(1-34)PTH (1-34)的半衰期短和生物利用率低。本研究制备了一种可生物降解的透明质酸-聚N-异丙基丙烯酰胺温敏水凝胶(AHA-g-PNIPAAm),并探究其作为药物载体对PTH (1-34)释放和细胞行为的影响。采用核磁共振氢谱和红外光谱对AHA-g-PNIPAAm的结构进行确证;利用物理溶胀法制备载药温敏水凝胶,并进行稳定性考察;采用扫描电镜观察水凝胶的形貌;采用紫外分光光度法考察水凝胶的最低临界转变温度和体外药物释放行为;四甲基偶氮唑盐微量酶反应比色法(MTT法)研究载药温敏水凝胶对小鼠单核巨噬细胞RAW264.7和小鼠颅骨前成骨细胞MC3T3-E1细胞的毒性与增殖作用;抗酒石酸酸性磷酸酶检测法考察载药水凝胶对RAW264.7分化的影响。结果显示,制备的载PTH (1-34)温敏水凝胶呈现规整的三维蜂窝状结构,具有良好的稳定性、温敏性和药物缓控释性能,可有效促进MC3T3-E1细胞的增殖,抑制RAW264.7向破骨细胞的分化。

     

    Abstract: The bone formation promoter recombinant human parathyroid hormone 1-34 PTH (1-34) has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.

     

/

返回文章
返回