目的 运用微流控技术制备天麻素（GAS）多囊脂质体（GAS-MVLs），考察GAS-MVLs在小鼠体内药动学及脑靶向性。方法 以成形性为评价指标，通过单因素实验筛选GAS-MVLs成形工艺；以包封率为指标，以药脂比（GAS∶卵磷脂）、醇脂比（胆固醇∶卵磷脂）、卵磷脂与三油酸甘油酯的质量比、聚山梨酯80的质量浓度为变量，正交试验优化GAS-MVLs处方；对GAS-MVLs进行包封率、粒径、聚合物分散性指数（PDI）、形态进行表征，进行体外累积释放率及初步稳定性试验。采用HPLC法测定小鼠给予GAS、GAS-MVLs（30 mg·kg^-1）后5、15、30、60、90、120、150、180、240、300 min血浆及脑组织中GAS的浓度，以相对摄取率（Re）、靶向效率（Te）及脑内峰浓度比（Ce）评价GAS-MVLs脑靶向性。结果 优化处方为药脂比为1∶2，醇脂比为1∶1，卵磷脂与三油酸甘油酯为1∶1.5，聚山梨酯80质量浓度为6%。精密称取处方量的卵磷脂、胆固醇、三油酸甘油酯溶于氯仿-乙醚（2∶1）混合溶剂为脂相，精密称取GAS溶于水作为内水相，内水相与脂相体积比为2∶3，将内水相加入到脂相中，在冰水浴下超声3 min，形成初乳；以6%聚山梨酯80为外水相，与初乳从不同入口注入微流控装置中，通过Y型芯片，设置总体积流量（18.78 mL·h^-1）和体积流量比（外水相∶初乳＝23∶1），经氮气去除有机溶剂，得GAS-MVLs。GAS-MVLs平均粒径为（2.09±0.14） μm，PDI为0.258±0.013，平均包封率为（34.47±0.39）%，分布均匀，形态圆整，结构致密。GAS在溶出介质中迅速溶解，6 h的释放量接近90%；GAS-MVLs在前6 h释放速度较快，随后接近平衡，72 h最大累积释放率在65%左右。稳定性试验中GAS-MVLs的平均粒径缓慢增大，包封率缓慢下降。药动学试验Re为5.70、Te为0.37、Ce为2.04。结论 采用微流控技术成功制备GAS-MVLs，可显著提高GAS的脑内富集程度。

Objective Microfluidic technology was used to prepare Gastrodin (GAS) multivesicular liposomes (GAS-MVLs), and to investigate the pharmacokinetic and brain targeting properties of GAS-MVLs in mice. Methods Using the formability as the evaluation index, a single-factor experiment was conducted to select the GAS-MVLs forming process; using the encapsulation rate as the index, the orthogonal experiment was conducted to optimize the GAS-MVLs formula with the variables of the ratio of GAS to lecithin, the ratio of cholesterol to lecithin, the ratio of lecithin to triolein, and the concentration of polyoxyethylene sorbitan monolaurate. The GAS-MVLs were characterized by encapsulation rate, particle size, polymer dispersion index (PDI), and morphology, and the in vitro cumulative release rate and initial stability were tested. The GAS concentration in the plasma and brain tissue of mice given GAS or GAS-MVLs (30 mg·kg^-1) at 5, 15, 30, 60, 90, 120, 150, 180, 240, and 300 min was determined by HPLC, and the brain targeting of GAS-MVLs was evaluated by relative uptake rate (Re), targeting efficiency (Te) and peak concentration ratio (Ce). Results The optimized formula was a ratio of GAS to lecithin of 1:2, a ratio of cholesterol to lecithin of 1:1, a ratio of lecithin to triolein of 1:2, and a concentration of polyoxyethylene sorbitan monolaurate of 6%. The egg yolk was prepared by dissolving the specified amount of lecithin, cholesterol, and triolein in a chloroform-ethanol (2:1) mixture as the lipid phase, and dissolving GAS in water as the internal aqueous phase. The internal aqueous phase was added to the lipid phase in a ratio of 2:3, and the mixture was sonicated for 3 minutes in an ice bath to form an emulsion. The external aqueous phase was prepared by adding 6% polyoxyethylene sorbitan monolaurate as the aqueous phase, and the emulsion and the external aqueous phase were injected from different inlets into a micro, by using a Y-type chip, the total volumetric flow rate (18.78 mL·h^-1) and the volume flow ratio (external aqueous phase : colloidal dispersion = 23 : 1) were set, and the organic solvent was removed by nitrogen, resulting in GAS-MVLs. The average particle size of GAS-MVLs was (2.09±0.14) μm, the PDI was (0.258±0.013), and the average encapsulation rate was (34.47±0.39)%. The distribution was uniform, the morphology was round and compact, and the structure was dense. GAS dissolved rapidly in the release medium, and the release amount after 6 hours was close to 90%. In the stability test, the average particle size of GAS-MVLs slowly increased, and the encapsulation rate slowly decreased. In the pharmacokinetics test, Re was 5.70, Te was 0.37, and Ce was 2.04. Conclusion The preparation of GAS-MVLs by microfluidic technology can significantly improve the degree of intracerebral enrichment of GAS, which lays the foundation for further development of GAS brain-targeted formulations.

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贵州省自然科学基金项目（贵州省科技基金-ZK［2021］-524）;贵州省卫健委科技基金项目（GZWKJ2022-233）