目的 制备大豆苷元（Dai）/磷脂复合物-壳聚糖纳米粒（Dai/PC-CS-NPs），系统考察其体内药动学特征及调血脂作用。方法 采用减压浓缩法制备大豆苷元/磷脂复合物（Dai/PC），结合单因素实验与Box-Behnken设计-效应面法优化Dai/PCCS-NPs的处方工艺；测定纳米粒的粒径、Zeta电位、包封率及载药量，采用X-射线粉末衍射法（XRPD）分析其晶型特征，通过透射电镜（TEM）观察其微观形貌；比较Dai、Dai/PC及Dai/PC-CS-NPs的饱和溶解度及体外释药行为。将SD大鼠随机分组，分别ig给予Dai、Dai/PC及Dai/PC-CS-NPs，比较各组主要药动学参数，计算Dai/PC及Dai/PC-CS-NPs相对于Dai的口服生物利用度。建立高脂血症大鼠模型，比较上述3种制剂对模型大鼠体质量、肝脏指数、血脂指标及肝功能指标的影响，采用苏木素-伊红（HE）染色观察肝脏病理形态学变化。结果 优化得到Dai/PC-CS-NPs的最佳处方为： Dai质量浓度1.03 mg·mL^-1，磷脂与壳聚糖质量比为5.89∶ 1，泊洛沙姆188质量分数为0.14%。该条件下制备的Dai/PC-CS-NPs，其包封率、载药量、粒径及Zeta电位分别为（83.01± 1.07）%、（12.60± 0.12）%、（198.87± 4.13） nm和（28.17± 0.59） mV。Dai在Dai/PC和Dai/PC-CS-NPs转变为无定形态，Dai/PC-CS-NPs外貌为类球形。Dai/PC和Dai/PC-CS-NPs极显著性提高了Dai在各pH磷酸盐缓冲液中溶解度，18 h累积释放率分别为50.47%和88.06%。以Dai为参比，Dai/PC及Dai/PCCS-NPs的相对口服生物利用度分别提高至1.92倍和5.67倍。调血脂实验显示，与Dai组（50 mg·kg^-1）比较，Dai/PCCS-NPs高剂量（50 mg·kg^-1）组体质量、肝脏指数、血脂指标及肝功能指标均得到极显著改善（P＜0.01），其治疗效果明显优于同剂量Dai/PC组。结论 Dai/PC及Dai/PC-CS-NPs均可显著提高Dai的口服生物利用度，并增强其调血脂作用，且Dai/PC-CS-NPs的改善效果更优。

Objective To prepare daidzein (Dai) /phospholipid complex-chitosan nanoparticles (Dai/PC-CS-NPs) and systematically investigate their in vivo pharmacokinetic characteristics and lipid-regulating effects. Methods Daidzein/phospholipid complex (Dai/PC) was prepared by vacuum concentration method. The prescription and process of Dai/PC-CS-NPs were optimized by single factor experiment and Box-Behnken design-response surface methodology. The particle size, Zeta potential, entrapment efficiency and drug loading of nanoparticles were determined. The crystal form characteristics were analyzed by X-ray powder diffraction (XRPD), and the microscopic morphology was observed by transmission electron microscopy (TEM). The saturated solubility and in vitro drug release behavior of Dai, Dai/PC and Dai/PC-CS-NPs were compared. SD rats were randomly divided into groups and ig administered with Dai, Dai/PC and Dai/PC-CS-NPs, respectively. The main pharmacokinetic parameters of each group were compared, and the oral bioavailability of Dai/PC and Dai/PC-CS-NPs relative to Dai was calculated. A hyperlipidemia rat model was established, and the effects of the three formulations on body weight, liver index, lipid parameters and liver function parameters of model rats were compared. The pathological morphological changes of the liver were observed by hematoxylin-eosin (HE) staining. Results The optimal prescription of Dai/PC-CS-NPs was obtained as follows: daidzein mass concentration 1.03 mg·mL^-1, mass ratio of phospholipid to chitosan 5.89∶ 1, and poloxamer 188 mass fraction 0.14%. Under these conditions, the entrapment efficiency, drug loading, particle size and Zeta potential of Dai/PC-CS-NPs were (83.01 ± 1.07) %, (12.60 ± 0.12) %, (198.87 ± 4.13) nm and (28.17 ± 0.59) mV, respectively. Daidzein transformed into amorphous form in Dai/PC and Dai/PC-CS-NPs, and the appearance of Dai/PC-CSNPs was spherical. Dai/PC and Dai/PC-CS-NPs significantly increased the solubility of daidzein in phosphate buffer solutions of various pH values. The cumulative release rates at 18 h were 50.47% and 88.06%, respectively. Compared with Dai (50 mg·kg^-1), the high-dose group of Dai/PC-CS-NPs (50 mg·kg^-1) significantly improved body weight, liver index, lipid parameters and liver function parameters (P<0.01), and its therapeutic effect was significantly better than that of the same dose of Dai/PC group. Conclusion Both Dai/PC and Dai/PC-CS-NPs can significantly increase the oral bioavailability of daidzein and enhance its lipid-regulating effect, and the improvement effect of Dai/PC-CS-NPs is better.

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河南省科技攻关计划项目（232102310026）；河南省社会科学界课题（SKL-2025-771）；河南省医学教育研究项目（WJLX2024237）