目的 制备负载五味子乙素的玉米醇溶蛋白/葡聚糖纳米粒（schisandrin B-loaded by zein-dextran nanoparticles，Sch B-zein/Dex-NPs），考察其体外释药行为及体内药动学行为。方法 采用反溶剂沉淀法制备Sch B-zein/Dex-NPs。单因素考察Sch B-zein/Dex-NPs影响因素，使用Box-Behnken设计-效应面法（Box-Behnken design-response surface method，BBD-RSM）优化Sch B-zein/Dex-NPs处方。透射电子显微镜（transmission electron microscopy，TEM）观察Sch B-zein/Dex-NPs形貌，傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）研究其结合机制，X射线粉末衍射（X-ray powder diffraction，XRPD）法分析五味子乙素晶型。测定Sch B-zein/Dex-NPs在纯化水、模拟胃液和模拟肠液中的饱和溶解度，透析袋法考察在模拟胃肠液中体外释药行为。SD大鼠分别ig给予五味子乙素和Sch B-zein/Dex-NPs粉末，计算其主要药动学参数。结果 Sch B-zein/Dex-NPs最佳处方为玉米醇溶蛋白质量浓度为19.5 g/L，反溶剂相与溶剂相体积比2.95∶1，葡聚糖质量浓度为5.0 g/L。包封率、载药量、粒径及ζ电位分别为（89.34±0.71）%、（4.91±0.05）%和（179.79±5.52）nm和（−32.16±0.69）mV，外貌为类球形。五味子乙素可能与玉米醇溶蛋白之间发生了氢键络合作用，五味子乙素以无定形态存在于Sch B-zein/Dex-NPs粉末中。Sch B-zein/Dex-NPs将五味子乙素在纯化水、模拟胃液和模拟肠液中溶解度分别增加至61.99、65.13和64.38倍。Sch B-zein/Dex-NPs在模拟胃、肠液中12 h累积释放率分别提高至71.68%和87.87%，释药行为均符合Weibull模型。药动学结果显示，Sch B-zein/Dex-NPs的达峰时间（t_max）延后至（2.08±0.46）h，半衰期（t_1/2）延长至（4.42±1.78）h，达峰浓度（C_max）和相对口服吸收生物利用度分别提高至3.82倍和4.36倍。结论 Sch B-zein/Dex-NPs包封率大于80%，显著增加了五味子乙素的溶解度、释放度及生物利用度，为后续研究奠定实验基础。

Objective To prepare schisandrin B-loaded by zein-dextran nanoparticles (Sch B-zein/Dex-NPs), and examine its in vitro drug release behavior and in vivo pharmacokinetic behavior. Methods Anti-solvent precipitation method was used to prepare Sch B-zein/Dex-NPs. Influencing factors were investigated by single factor experiments, Box-Behnken design-response surface method (BBD-RSM) was employed to optimize prescriptions of Sch B-zein/Dex-NPs. Transmission electron microscope (TEM) was employed to observe the microscopic appearance of Sch B-zein/Dex-NPs, Fourier transform infrared spectrometer (FTIR) was used to study binding mechanism, X-ray powder diffraction (XRPD) was employed to analyze the crystal form of schisandrin B in Sch B-zein/Dex-NPs powder. Saturated solubility of Sch B-zein/Dex-NP powder was determined in distilled water, simulated gastric fluids and simulated intestinal fluids, and the in vitro drug release in simulated gastrointestinal fluids was investigated by dialysis bag method. SD rats were administered intragastrically with schisandrin B and Sch B-zein/Dex-NPs respectively, and main pharmacokinetic parameters were calculated. Results Optimal formulations of Sch B-zein/Dex-NPs: mass concentration of zein was 19.5 g/L, volume ratio of anti-solvent phase to solvent phase was 2.95:1 and mass concentration of dextran was 5.0 g/L. The envelopment efficiency, drug loading, particle size and ζ potential were (89.34 ±0.71)%, (4.91 ±0.05)%, (179.79 ±5.52) nm and (−32.16 ±0.69) mV, respectively. Appearance of Sch B-zein/Dex-NPs were spheroidal. Schisandrin B might complex with zein by hydrogen bond. The state of schisandrin B changed into an amorphous form in Sch B-zein/Dex-NPs powder. Sch B-zein/Dex-NPs increased the solubility of schisandrin B in distilled water, simulated gastric fluids and simulated intestinal fluids by 61.99, 65.13, and 64.38 times, respectively. Cumulative drug release of Sch B-zein/Dex-NPs in simulated gastric and intestinal fluids increased to 71.68% and 87.87% in 12 h, and the drug release behavior was both in accordance with Weibull model. Pharmacokinetic results showed that the t_max of Sch B-zein/Dex-NPs was postponed to (2.08 ±0.46) h, t_1/2 was prolonged to (4.42 ±1.78) h. C_max and relative oral bioavailability were increased to 3.82 and 4.36 times, respectively. Conclusion Encapsulation efficiency of Sch B-zein/Dex-NPs was more than 80%, and significantly increased the solubility, release rate and bioavailability of schisandrin B, which laid an experimental foundation for subsequent research.

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河南省重点研发推广项目（222102310082）；河南省科技研发计划联合基金项目（301420098）