目的 以肉豆蔻酸异丙酯（IPM）为油相构建自乳化递送系统（IPM@SEDDS），优选IPM@SEDDS最佳处方并评价其蛋白晕（PC）结合能力。方法 结合伪三元相图法和星点设计-响应面法筛选IPM@SEDDS的最佳处方，评价其外观、粒径、ζ电位和稳定性；通过CCK-8、溶血实验考察其安全浓度范围及生物相容性；利用粒径结合考马斯亮蓝染色评估IPM@SEDDS在血清中的PC形成能力。结果 IPM@SEDDS最佳乳化剂和助乳化剂分别为聚山梨酯-80和无水乙醇，混合乳化剂质量比为2∶ 1，油相与混合乳化剂质量比为3∶ 7，涡旋状态下逐滴加入纯水至10 mL，得半透明状带有淡蓝色乳光的IPM@SEDDS。IPM@SEDDS粒径为（209.77±6.34） nm，ζ电位为（-16.20±1.36） mV，且其具有良好的细胞安全范围和血液相容性。体外PC孵育实验结果表明，IPM@SEDDS与胎牛血清（FBS）、小鼠血清（MS）、小鼠炎症血清（iMS）之间形成了PC，且PC的形成能力与孵育时间、血清浓度以及血清种类有关。结论 IPM@SEDDS具有较好的药剂学性能，安全性高且生物相容性好，可以为IPM更为广泛的应用提供实验参考。

Objective To construct a self-emulsifying drug delivery system (SEDDS) based on isopropyl myristate (IPM), optimize the formulation of IPM@SEDDS, and evaluate its protein corona (PC) binding ability. Methods The optimal formulation of IPM@SEDDS was screened by pseudo-ternary phase diagram and central composite design-response surface methodology. The appearance, particle size, ζ potential and stability of IPM@SEDDS were evaluated. The safe concentration range and biocompatibility of IPM@SEDDS were investigated by CCK-8 and hemolysis experiments. The formation ability of IPM@SEDDS PC was evaluated by particle size combined with coomassie brilliant blue staining. Results The optimal emulsifier and co-emulsifier for IPM@SEDDS were Tween-80 and anhydrous ethanol, the mass ratio of mixed emulsifier is 2∶1, the mass ratio of oil phase to mixed emulsifier is 3∶7, IPM@SEDDS was obtained by adding pure water dropwise to 10 mL under vortexing, presenting a semi-transparent state with a light blue milky luster. The particle size of IPM@SEDDS was (209.77 ±6.34) nm, the ζ potential was (-16.20 ±1.36) mV, moreover, it has good cell safety range and blood compatibility. The results of in vitro PC incubation experiments show that IPM@SEDDS forms PC with fetal bovine serum (FBS), mouse serum (MS), and mouse inflammatory serum (iMS), and the formation ability of PC is related to the incubation time, serum concentration, and serum type. Conclusion IPM@SEDDS has excellent pharmaceutical properties, high safety and good biocompatibility, which can provide experimental references for the more extensive application of IPM.

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国家自然科学基金资助项目（ 82260827）；贵州省科技计划项目黔科合基础-ZK[2022]380；贵州省科技创新基地，黔科合中引地[2023]003；贵州省高层次创新型人才百层次人才/黔科合平台人才-GCC[2023]048；贵州医科大学国家自然科学基金培育项目（ 20NSP050）；贵州医科大学高层次人才科研启动基金项目校博合 J 字（2023） 026 号。