目的 优化吴茱萸碱纳米结构脂质载体（evodiamine nanostructured lipid carriers，Evo-NLC）处方，研究SD大鼠体内口服药动学特征。方法 高压均质法制备Evo-NLC。单因素考察结合Box-Behnken响应面法优化Evo-NLC处方并进行表征，透析法考察体外释药情况。按照100 mg/kg剂量ig后采血，HPLC法测定血药浓度，计算吴茱萸碱和Evo-NLC的主要药动学参数。结果 制备的Evo-NLC外观为淡蓝色乳光的透明液体。最佳处方为吴茱萸碱用量为64.13 mg，固-液脂质比为4.34∶1，表面活性剂用量为1.15%。测得Evo-NLC平均包封率为（87.84±1.62）%，平均粒径为（152.62±9.43）nm，Zeta电位为（−；36.67±1.93）mV，载药量为（5.96±0.22）%。体外释药过程符合Weibull模型lnln[1/（1－M_t/M_∞）]＝0.514 4 lnt－1.311 2。口服药动学结果显示，与吴茱萸碱原料药相比，Evo-NLC的口服相对生物利用度提高至4.47倍。结论Box-Behnken响应面法所建立的模型可用于Evo-NLC处方优化，Evo-NLC有效提高了吴茱萸碱的相对口服吸收生物利用度。

Objective To optimize formulations of evodiamine nanostructured lipid carriers (Evo-NLC), and study its pharmacokinetic characteristics in SD rats after gastric administration. Methods High pressure homogenization was used to prepare Evo-NLC. Single factor investigation and Box-Behnken design-response surface method was employed to optimize the formulations of Evo-NLC. Dialysis method was used to study drug release of Evo-NLC. Blood samples were collected after gastric administration at a dose of 100 mg/kg. HPLC method was adopted in the plasma concentration determination, and then calculated main pharmacokinetic parameters of evodiamine and Evo-NLC. Results The prepared Evo-NLC were transparent liquid with light blue opalescence. Optimal formulations: evodiamine dose was 64.13 mg, ratio of solid to liquid lipid was 4.34:1 and surfactant concentration was 1.15%. Average entrapment efficiency was (87.84 ±1.62)%, particle size was (152.62 ±9.43) nm, Zeta potential was (−36.67 ±1.93) mV and drug loading was (5.96 ±0.22)%. The drug release process conformed to Weibull model: lnln[1/(1－M_t/M_∞)]＝0.514 4 lnt－1.311 2. Resultsof oral pharmacokinetic showed that relative bioavailability of Evo-NLC were increased to 4.47 times compare to evodiamine. Conclusion The model established by Box-Behnken design-response surface could be employed to optimize the formulation of Evo-NLC, and increased the relative bioavailability of evodiamine greatly.

R283.6

国家重大科技专项（2018ZX09200109-002-009）；河南省二〇二一年科技发展计划（212102310315）