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

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