目的 以肉豆蔻酸異丙酯（IPM）為油相構(gòu)建自乳化遞送系統(tǒng)（IPM@SEDDS），優(yōu)選IPM@SEDDS最佳處方并評價其蛋白暈（PC）結(jié)合能力。方法 結(jié)合偽三元相圖法和星點設(shè)計-響應(yīng)面法篩選IPM@SEDDS的最佳處方，評價其外觀、粒徑、ζ電位和穩(wěn)定性；通過CCK-8、溶血實驗考察其安全濃度范圍及生物相容性；利用粒徑結(jié)合考馬斯亮藍染色評估IPM@SEDDS在血清中的PC形成能力。結(jié)果 IPM@SEDDS最佳乳化劑和助乳化劑分別為聚山梨酯-80和無水乙醇，混合乳化劑質(zhì)量比為2∶ 1，油相與混合乳化劑質(zhì)量比為3∶ 7，渦旋狀態(tài)下逐滴加入純水至10 mL，得半透明狀帶有淡藍色乳光的IPM@SEDDS。IPM@SEDDS粒徑為（209.77±6.34） nm，ζ電位為（-16.20±1.36） mV，且其具有良好的細胞安全范圍和血液相容性。體外PC孵育實驗結(jié)果表明，IPM@SEDDS與胎牛血清（FBS）、小鼠血清（MS）、小鼠炎癥血清（iMS）之間形成了PC，且PC的形成能力與孵育時間、血清濃度以及血清種類有關(guān)。結(jié)論 IPM@SEDDS具有較好的藥劑學(xué)性能，安全性高且生物相容性好，可以為IPM更為廣泛的應(yīng)用提供實驗參考。

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.

R283.6

國家自然科學(xué)基金資助項目（ 82260827）；貴州省科技計劃項目黔科合基礎(chǔ)-ZK[2022]380；貴州省科技創(chuàng)新基地，黔科合中引地[2023]003；貴州省高層次創(chuàng)新型人才百層次人才/黔科合平臺人才-GCC[2023]048；貴州醫(yī)科大學(xué)國家自然科學(xué)基金培育項目（ 20NSP050）；貴州醫(yī)科大學(xué)高層次人才科研啟動基金項目校博合 J 字（2023） 026 號。