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刘庆祖, 刘建恒, 王润生, 刘义灏, 杨慧恺, 毛克亚. 聚乙二醇化锌铁氧磁性纳米颗粒对咪喹莫特的载药性能及细胞毒性研究[J]. 解放军医学院学报, 2021, 42(4): 444-450. DOI: 10.3969/j.issn.2095-5227.2021.04.016
引用本文: 刘庆祖, 刘建恒, 王润生, 刘义灏, 杨慧恺, 毛克亚. 聚乙二醇化锌铁氧磁性纳米颗粒对咪喹莫特的载药性能及细胞毒性研究[J]. 解放军医学院学报, 2021, 42(4): 444-450. DOI: 10.3969/j.issn.2095-5227.2021.04.016
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LIU Qingzu, LIU Jianheng, WANG Runsheng, LIU Yihao, YANG Huikai, MAO Keya. Drug-loading properties and toxicity of imiquimod-loaded zinc ferrite magnetic nanoparticle[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(4): 444-450. DOI: 10.3969/j.issn.2095-5227.2021.04.016
Citation: LIU Qingzu, LIU Jianheng, WANG Runsheng, LIU Yihao, YANG Huikai, MAO Keya. Drug-loading properties and toxicity of imiquimod-loaded zinc ferrite magnetic nanoparticle[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2021, 42(4): 444-450. DOI: 10.3969/j.issn.2095-5227.2021.04.016
shu

聚乙二醇化锌铁氧磁性纳米颗粒对咪喹莫特的载药性能及细胞毒性研究

Drug-loading properties and toxicity of imiquimod-loaded zinc ferrite magnetic nanoparticle

    摘要
  • 摘要:
      背景  超顺磁性铁氧纳米颗粒是特殊的磁性纳米颗粒，粒径为1～100 nm，由于其磁响应性高、比表面积大、生物相容性好、毒性低而广泛应用于生物医学和临床研究。
      目的  通过对高温有机溶剂法合成的锌铁氧体磁性纳米颗粒进行表面修饰，研究其对咪喹莫特的载药性能及生物相容性。
      方法  利用逆向蒸发法将聚乙二醇(polyethylene glycol，PEG)以及咪喹莫特(imiquimod，R837)修饰至锌铁氧体表面，并进一步在表面修饰叶酸(folic acid，FA)，构建磁性纳米载药复合系统，并对复合纳米材料系统的结构、形貌和性能进行表征。使用高效液相色谱法对该系统的载药性能进行评价；使用CCK-8法检测该复合纳米颗粒载药对小鼠胚胎成纤维细胞(mouse embryonic fibroblast，MEF)和人骨肉瘤细胞MG-63的生物毒性。
      结果  PEG、R837成功修饰至锌铁氧体表面，该复合纳米材料系统载药率为4.40%，包封率为87.90%，并可进一步在表面修饰叶酸。药物缓释测试，6 h时，37℃条件下释放量达到27.31%，43℃条件下释放量达到45.86%。测试Zn0.3Fe2.7O4-PEG-R837性能及其对MEF、MG-63两种细胞系的生物毒性，孵育48 h后，在600 μg/mL以下未出现细胞毒性。
      结论  合成的Zn0.3Fe2.7O4-PEG-R837复合磁性纳米载药系统具有良好的形貌、载药性能以及较低的细胞毒性。

     

    Abstract:
      Background  Superparamagnetic iron oxide nanoparticles (SPIONs) are special magnetic nanoparticles with a particle size of 1-100 nm. Due to their high magnetic response, large specific surface area, good biocompatibility, and low toxicity, they are widely used in biomedical and clinical research.
      Objective  To study the drug-carrying performance and in vitro biocompatibility of Zn0.3Fe2.7O4 magnetic nanoparticles synthesized by high-temperature organic solvent method loaded with imiquimod.
      Methods  Polyethylene glycol (PEG) and imiquimod (R837) were fabricated on the surface of Zn0.3Fe2.7O4 by reverse evaporation method, and folic acid (FA) was further modified on the surface to construct a magnetic nano-drug carrier composite system. Using X-ray diffraction (XRD), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), dynamic light scattering (DLS), etc, the structure, morphology and performance of the composite nanomaterial system were analyzed. The drug-carrying performance of the system was evaluated using HPCL. CCK8 assay was used to detect the toxicity of the composite nanoparticles on mouse embryonic fibroblast cells (MEF) and human osteosarcoma MG63 cells.
      Results  PEG and R837 were successfully modified to the surface of Zn0.3Fe2.7O4. The drug loading rate of the composite nanomaterial system was 4.40%, the encapsulation rate was 87.90%, and the folic acid was further modified on the surface. In the sustained release test of the drug, the release amount reached 27.31% with the temperature of 37℃ at 6 h, and 45.86% with the temperature of 43℃. Zn0.3Fe2.7O4-PEG-R837 and its biological toxicity to MEF, MG63 were tested. After 48 h incubation, there was no toxicity with the concentration below 600μg/mL.
      Conclusion  The synthesized Zn0.3Fe2.7O4-PEG-R837 composite magnetic nano-drug carrier system has good drug-carrying performance and low toxity.

     

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