目的 制备包载金丝桃苷的磷脂酰胆碱/壳聚糖自组装纳米粒（hyperoside self-assembled phosphatidylcholine chitosan nanoparticles，Hyp-PC/CS-NPs），并考察相对口服吸收生物利用度。方法 单因素考察Hyp-PC/CS-NPs制备的主要影响因素，使用Box-Behnken设计-效应面法筛选Hyp-PC/CS-NPs处方。透射电子显微镜（transmission electron microscope，TEM）观察Hyp-PC/CS-NPs形貌；制备Hyp-PC/CS-NPs冻干粉并测定其饱和溶解度；傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）研究Hyp-PC/CS-NPs冻干粉及各组分的结合机制；X射线粉末衍射法（X-ray powder diffraction，XRPD）分析金丝桃苷晶型；考察Hyp-PC/CS-NPs冻干粉及金丝桃苷原料药的体外释药行为；测定Hyp-PC/CS-NPs冻干粉的沉降率并考察其储存稳定性。SD大鼠分别ig给予金丝桃苷原料药和Hyp-PC/CS-NPs冻干粉，考察其口服药动学行为，并计算Hyp-PC/CS-NPs相对口服生物利用度。结果 Hyp-PC/CS-NPs最佳处方：药物质量浓度为0.37 mg/mL，磷脂酰胆碱与壳聚糖质量比为16.3∶1，磷脂酰胆碱与金丝桃苷质量比为7.9∶1。Hyp-PC/CS-NPs的包封率、载药量、粒径及ζ电位分别为（84.19±1.23）%、（8.81±0.16）%、（166.18±4.03）nm和（32.39±0.95）mV；Hyp-PC/CS-NPs外貌为类球形，金丝桃苷可能与载体发生了氢键络合作用；金丝桃苷以无定型形态存在于Hyp-PC/CS-NPs冻干粉中；与原料药相比，Hyp-PC/CS-NPs冻干粉中的金丝桃苷在模拟胃液、蒸馏水和模拟肠液中的饱和溶解度分别增加了7.22、4.04、5.10倍。药动学结果显示，与金丝桃苷原料药或物理混合物相比，Hyp-PC/CS-NPs药动学参数均极显著性增加（P＜0.01）；Hyp-PC/CS-NPs中金丝桃苷相对口服生物利用度增加至其原料药的4.11倍。结论 成功制备了Hyp-PC/CS-NPs及其冻干粉，Hyp-PC/CS-NPs明显改变了金丝桃苷的体内药动学行为，显著增加了其口服生物利用度，为其后续药效学评价奠定实验基础。

Objective To prepare hyperoside self-assembled phosphatidylcholine chitosan nanoparticles (Hyp-PC/CS-NPs), and relative oral bioavailability were studied. Methods The main influencing factors of Hyp-PC/CS-NPs were investigated by single factor experiments, Box-Behnken design-response surface method was employed to optimize prescriptions of Hyp-PC/CS-NPs. Transmission electron microscope (TEM) was employed to observe microscopic appearance of Hyp-PC/CS-NPs, lyophilized powder of Hyp-PC/CS-NPs was prepared and its saturated solubility was determined, Fourier transform infrared spectroscopy (FTIR) was used to investigate the binding mechanism of Hyp-PC/CS-NPs lyophilized powder and each component, and crystal form of hyperoside was analyzed by X-ray powder diffraction (XRPD). Drug release behavior in vitro of Hyp-PC/CS-NPs lyophilized powder and hyperoside was determined, the sedimentation rate of Hyp-PC/CS-NPs lyophilized powder was determined and its storage stability was also investigated. SD rats were administered intragastrically with hyperoside and Hyp-PC/CS-NPs lyophilized powder, its oral pharmacokinetic behavior was studied, and relative oral bioavailability of Hyp-PC/CS-NPs was calculated. Results Optimal formulations of Hyp-PC/CS-NPs: hyperoside concentration was 0.37 mg/mL, phosphatidylcholine to chitosan ratio was 16.3:1, phosphatidylcholine to hyperoside ratio was 7.9:1. Envelopment efficiency, drug loading, particle size and ζ potential were (84.19 ±1.23)%, (8.81 ±0.16)%, (166.18 ±4.03) nm and (32.39 ±0.95) mV, respectively. Appearance of Hyp-PC/CS-NPs was spherical, hyperoside may have complexed with the carrier by hydrogen bond. The state of hyperoside changed into an amorphous form in Hyp-PC/CS-NPs freeze-dried powder. Solubility of hyperoside in simulated gastric juice, distilled water and simulated intestinal juice was increased by 7.22, 4.04 and 5.10 times, respectively. Pharmacokinetic results showed that the pharmacokinetic parameters of Hyp-PC/CS-NPs were significantly increased compared with hyperoside or physical mixture (P < 0.01), and the relative bioavailability of hyperoside in Hyp-PC/CS-NPs was increased to 4.11 times. Conclusion Hyp-PC/CS-NPs and its lyophilized powder were successfully prepared, pharmacokinetic behavior of hyperoside in vivo was greatly changed, and bioavailability of hyperoside was significantly increased by Hyp-PC/CS-NPs, which established the experimental foundation for the follow-up pharmacodynamic evaluation.

R283.6

河南省高等学校重点科研项目计划（23B310010）;河南省医学教育研究项目（WJLX2023153）;黑龙江省重点研发计划（GA22C004）