目的 制备蒙花苷巯基化纳米胶束（buddleoside sulfhydryl-modified nanomicelles，Bud-SH-NMs），考察口服药动学行为。方法 薄膜分散-超声法制备Bud-SH-NMs，单因素实验结合Box-Behnken设计-效应面法（Box-Behnken design-response surface methodology，BBD-RSM）优化处方。X射线粉末衍射法（XRPD）分析晶型，透射电子显微镜（TEM）观察Bud-SH-NMs外貌形态，透析法考察在pH 2.0和pH 6.8磷酸盐缓冲液（PBS）中的释药行为。SD大鼠分别ig给予蒙花苷混悬液和Bud-SH-NMs冻干粉，HPLC法测定血药浓度，计算主要药动学参数。结果 Bud-SH-NMs最佳处方：巯基修饰二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG₂₀₀₀-SH）与药物用量比为7.5∶1，水合体积为9.7 mL，水合温度45 ℃。Bud-SH-NMs的包封率、载药量、沉降率、粒径和ζ电位分别为（90.86±1.78）%、（10.76±0.24）%、（4.14±0.29）%、（49.27±6.82）nm和（−18.53±1.12）mV。蒙花苷在Bud-SH-NMs冻干粉中以无定型形式存在，微观外貌为球形，在pH 2.0和pH 6.8 PBS中缓释特征明显，释药过程符合Weibull模型。药动学结果显示，Bud-SH-NMs半衰期（t_1/2）增加至（5.93±0.96）h，血药浓度（C_max）和相对口服吸收生物利用度分别提高至2.83倍和5.10倍。结论 Bud-SH-NMs粒径小，包封率高，稳定性好，显著促进了蒙花苷口服吸收，为后续研究奠定基础。

Objective To prepare buddleoside sulfhydryl-modified nanomicelles (Bud-SH-NMs) and investigate their oral pharmacokinetic behavior in vivo. Methods Bud-SH-NMs were prepared by thin film dispersion-ultrasonic method. Single factor experiments combined with Box-Behnken response surface design method was used to optimize the prescriptions. Crystal form of Bud-SH-NMs lyophilized powder was analyzed by X-ray powder diffraction (XRPD), and the appearance was observed using transmission electron microscope (TEM). The release behavior of Bud-SH-NMs in pH 2.0 and pH 6.8 phosphate buffers were investigated by dialysis method. SD rats in each group were administered intragastrically with buddleoside suspension and Bud-SH-NMs lyophilized powder, respectively. The concentration of buddleoside in plasma was analyzed by HPLC, and main pharmacokinetic parameters were calculated. Results The optimal formulation of Bud-SH-NMs was as follows: DSPE-PEG₂₀₀₀-SH to drug ratio of 7.5:1, hydration volume of 9.7 mL, and hydration temperature of 45 ℃. Envelopment efficiency, drug loading, settlement rate, particle size and ζ potential were (90.86 ± 1.78)%, (10.76 ± 0.24)%, (4.14 ± 0.29)%, (49.27 ± 6.82) nm and (−18.53 ± 1.12) mV, respectively. Buddleoside existed in an amorphous form in Bud-SH-NMs lyophilized powder, and its microscopic appearance was spherical. Sustained release characteristics of Bud-SH-NMs were obvious in pH 2.0 and pH 6.8 phosphate buffer, and drug release process conformed to Weibull model. Pharmacokinetic results showed that t_1/2 of Bud-SH-NMs was increased to (5.93 ± 0.96) h, C_max and oral relative bioavailability was increased to 2.83-fold and 5.10-fold, respectively.. Conclusion Bud-SH-NMs had small particle size, high entrapment efficiency and good stability, and promoted oral absorption of buddleoside effectively, which laid the foundation for the following research.

R283.6

2023年度河南省高等学校重点科研项目（23B320013）；河南应用技术职业学院青年骨干教师 资助项目（2020-GGJS-Y003）