目的 制备香菇多糖-蒙花苷自组装纳米粒（lentinan-buddleoside self-assembled nanoparticles，Len-Bud-SANs），考察理化性质及口服药动学行为，并评价急性毒性。方法 采用自组装法制备Len-Bud-SANs。以包封率、载药量和粒径为指标，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Len-Bud-SANs处方工艺。透射电子显微镜（transmission electron microscope，TEM）观察Len-Bud-SANs外貌形态，X射线粉末衍射（X-ray powder diffraction，XRPD）法分析Len-Bud-SANs粉末晶型。分子模拟对接和傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）研究香菇多糖和蒙花苷结合机制。测定Len-Bud-SANs在pH 2.0和pH 6.8磷酸盐缓冲液（PBS）中溶解度及释药行为。SD大鼠分别ig给予蒙花苷和Len-Bud-SANs粉末，HPLC法测定血药浓度，计算主要药动学参数。以体质量、摄食量、胸腺指数和脾脏指数为指标，对Len-Bud-SANs粉末进行安全性评价。苏木精-伊红（HE）染色观察SD大鼠重要器官病理情况。结果 Len-Bud-SANs最佳处方：香菇多糖质量分数为0.39%，制备温度为65.00℃，制备时间为1.50 h。Len-Bud-SANs的包封率、载药量、粒径和ζ电位分别为（88.57±0.83）%、（8.02±0.11）%、（57.54±4.90）nm和（-32.10±1.36）mV。Len-Bud-SANs微观外貌为球形，蒙花苷在Len-Bud-SANs粉末中转变为无定形态。Len-Bud-SANs在pH 2.0和pH 6.8 PBS中溶解度分别提高至59.89倍和42.95倍，累积释放率分别提高至90.80%和91.73%，释药过程符合Weibull模型。药动学结果显示，Len-Bud-SANs半衰期（t_1/2）增加至（4.45±0.80）h，血药浓度（C_max）和时间曲线下面积（AUC_0～t）分别提高至3.00倍和5.60倍。与空白组相比，Len-Bud-SANs组体质量、摄食量、胸腺指数、脾脏指数及重要器官病理均无明显变化。结论 Len-Bud-SANs显著促进了蒙花苷口服吸收，未见明显毒性，为后续开发研究奠定基础。

Objective To prepare lentinan-buddleoside self-assembled nanoparticles (Len-Bud-SANs), and evaluate investigate its physicochemical properties, oral pharmacokinetic behavior and acute toxicity. Methods Len-Bud-SANs were prepared by self-assembled method. Envelopment efficiency, drug loading and particle size were employed as indicators, single factor experiments combined with Box-Behnken design-response surface method (BBD-RSM) were used to obtainoptimal prescriptions of Len-Bud-SANs. The appearance of Len-Bud-SANs was observed by transmission electron microscope (TEM) was, crystal form of Len-Bud-SANs powder was analyzed by X-ray powder diffraction (XRPD). Molecular simulation docking and Fourier transform infrared spectroscopy (FTIR) were used to study the binding mechanism between lentinan and buddleoside. The solubility and drug release behavior of Len-Bud-SANs were determined in phosphate buffer solution (PBS) at pH 2.0 and pH 6.8. SD rats in each group were administered intragastrically with buddleoside suspension and Len-Bud-SANs powder, then buddleoside concentration in plasma was analyzed by HPLC method, and main pharmacokinetic parameters were calculated. Safety evaluation of Len-Bud-SANs powder was performed by indicators of body weight, food intake, thymus index and spleen index. Pathological conditions of the important organs were observed by hematoxylin-eosin (HE) staining. Results Optimal formulation of Len-Bud-SANs: mass fraction of lentinan was 0.39%, preparation temperature was 65.00 ℃, and preparation time was 1.50 h. Envelopment efficiency, drug loading, particle size and ζ potential were (88.57 ±0.83)%, (8.02 ±0.11)%, (57.54 ±4.90) nm and (−32.10 ±1.36) mV, respectively. Microscopic appearance of Len-Bud-SANs was spherical, and buddleoside existed as an amorphous form in Len-Bud-SANs powder. Solubility of Len-Bud-SANs in phosphate buffer solution of pH 2.0 and pH 6.8 was increased to 59.89 times and 42.95 times, and cumulative release rate were increased to 90.80% and 91.73%, respectively. Drug release behavior of Len-Bud-SANs conformed to Weibull model. Oral pharmacokinetic results showed that t_1/2 of Len-Bud-SANs was increased to (4.45 ±0.80) h, C_max and AUC_0-t were increased to 3.00-fold and 5.60-fold. Compared with the blank group, there was no significant change in body weight, food intake, thymus index, spleen index and pathology of important organs in the Len-Bud-SANs group. Conclusion Len-Bud-SANs significantly promoted oral absorption of buddleoside effectively, and no obvious toxicity was observed, which laid the foundation for subsequent research and development.

R283.6

新疆维吾尔自治区“天池英才”引进计划（XJGXJGZH-2024032）；2025年校级重点培育科研项目（2025-XJKY-06）；新疆科技学院科研基金创新团队专项（2024-KYTD02）