吴茱萸碱纳米结构脂质载体处方优化和SD大鼠体内口服药动学研究  

Optimization of evodiamine nanostructured lipid carriers and oral pharmacokinetics study in SD rats

作　　者：董丹丹[1] 焦红军[1] 郝海军 范明松 DONG Dan-dan;JIAO Hong-jun;HAO Hai-jun;FAN Ming-song(Department of Pharmacy,The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Technique Center,Shanghai Leiyunshang Pharmaceutical Co.,Ltd.,Shanghai 201401,China)

机构地区：[1]郑州大学第二附属医院药学部,河南郑州450000 [2]上海雷允上药业有限公司技术中心,上海201401

出　　处：《中草药》2022年第1期60-70,共11页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：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;/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-Mt/M∞)]=0.514 4 lnt-1.311 2. Results of 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 EvoNLC, and increased the relative bioavailability of evodiamine greatly.

关 键 词：吴茱萸碱 纳米结构脂质载体 Box-Behnken响应面法 缓释 药动学 相对生物利用度 透析法 Weibull模型 

分 类 号：R283.6[医药卫生—中药学]