Abstract:

Objective To investigate the preparation method of tacrolimus/mycophenolate mofetil dualdrug nanoparticles supported by PEG-PLGA and its application value in immunosuppression. Methods Tacrolim us/mycophenolate mofetil supported PEG-PLGA nanoparticles were prepared by phacoemulsification - solvent evaporation method. Their morphology was observed by transmission electron microscopy， and their particle size and distribution were detected by Malvern particle size analyzer. The successful synthesis of nanoparticles was verified by infrared spectroscopy. Furthermore， the immunosuppressive effects of different drug ratios were evaluated in an in vitro T cell activation and proliferation model. Results The prepared dual-drug nanoparticles were in regular spherical shape， with an average particle size of approximately 258 nm and uniform dispersion. Infrared spectroscopy confirmed the successful binding of the drug to the carrier. Cell experiments have shown that the inhibitory effect on T cell proliferation is the best when thedual-drug ratio （tacrolimus ：mycophenolate mofetil） is 1 ：3.5. Meanwhile， this dual-drug nanoparticle can significantly down-regulate the expression of activation markers of T cells， and its inhibitory effect is superior to that of the singledrug nanoparticles of each component. Conclusion PEG-PLGA-loaded tacrolimus/mycophenolate mofetil dual-drug nanoparticles have good physicochemical properties and significant immunosuppressive activity. They are expected to beused as candidate preparations for hormone reduction and discontinuation and long-term immune maintenance therapy after liver transplantation， and have important clinical application prospects. 

Key words:

Liver transplantation； , PEG-PLGA nanoparticles； , Tacrolimus； , Mycophenolate mofetil； , Immunosuppression

摘要：

目的 考察一种以 PEG-PLGA 为载体的他克莫司 / 吗替麦考酚酯双药纳米粒的制备方法及其在免疫抑制中的应用价值。方法 采用超声乳化 - 溶剂蒸发法制备他克莫司 / 吗替麦考酚酯负载的 PEG-PLGA纳米粒，通过透射电子显微镜观察其形貌，并通过马尔文粒度仪检测其粒径及分布 ；采用红外光谱验证纳米粒的成功合成。进一步，在体外 T 细胞活化与增殖模型中评估不同药物配比的免疫抑制效果。结果 所制备的双药纳米粒呈规则球形，平均粒径约为 258 nm，分散均匀。红外光谱证实了药物与载体的成功结合。细胞实验显示，在双药配比为他克莫司 ：吗替麦考酚酯＝ 1 ：3.5 时，对 T 细胞增殖的抑制效果最佳。同时，该双药纳米粒可显著下调 T 细胞的活化标志物表达，其抑制作用优于各组分的单药纳米粒。结论 PEG-PLGA 负载的他克莫司 / 吗替麦考酚酯双药纳米粒具有良好的理化性质和显著的免疫抑制活性，有望作为肝移植术后激素减停及长期免疫维持治疗的候选制剂，具有重要的临床应用前景。

关键词:

 , 肝移植 ； , PEG-PLGA 纳米粒 ； 他克莫司 ； 吗替麦考酚酯 ； 免疫抑制