目的 构建花旗松素磷脂复合物白蛋白纳米粒（taxifolin phospholipid complex albumin nanoparticles，Tax-PC/BSA NPs）并优化其制备工艺，考察其肠吸收特性。方法 采用溶剂挥发法和新型白蛋白纳米粒制备技术（Nab^TM技术）制备花旗松素磷脂复合物白蛋白纳米粒。采用Box-Behnken设计-响应面法（Box-Behnken design-response surface method，BBD-RSM），优化其制备工艺并验证；以透射电子显微镜（transmission electron microscope，TEM）、粒径、多分散指数（polydispersity index，PDI）、ζ电位、差示扫描量热法（differential scanning calorimetry，DSC）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FT-IR）及X射线衍射（X-ray diffraction，XRD）技术对Tax-PC/BSA NPs进行表征，测定理化性质并考察制剂稳定性；体外模拟消化释放，探讨制剂在人体消化环境的释放规律；大鼠在体单向肠灌流模型评价Tax-PC/BSA NPs肠吸收特性。结果 Tax-PC/BSA NPs的最优制备工艺为药脂比1∶3，药/BSA比1∶9.39，油水比1∶11.51，超声时间7.76 min；3次验证实验结果显示，Tax-PC/BSA NPs的包封率为（86.14±0.38）%，载药量为（7.27±0.03）%，渗漏率为（0.87±0.04）%。按优化后工艺所制Tax-PC/BSA NPs在TEM下呈类球状，平均粒径为（184.90±0.98）nm、PDI为0.275±0.010、ζ电位为（-36.6±0.53）mV，DSC、FT-IR、XRD进一步验证了Tax-PC/BSA NPs的形成；Tax-PC/BSA NPs溶解度相较花旗松素提高了38.48倍，lgP值>1，脂溶性明显提高；Tax-PC/BSA NPs冻干粉在4℃下存放3个月稳定性良好；花旗松素、Tax-PC、Tax-PC/BSA NPs累积释放率分别为（48.26±0.71）%、（71.86±1.83）%、（82.73±0.62）%；Tax-PC/BSA NPs、Tax-PC和花旗松素在各肠段均有吸收，主要吸收部位分别为十二指肠和空肠，Tax-PC/BSA NPs的吸收速率常数和表观吸收系数均显著高于Tax-PC和花旗松素（P<0.05、0.01）。结论 优化所得Tax-PC/BSA NPs制备工艺稳定、可行；所制Tax-PC/BSA NPs有效提高药物的脂溶性、水溶性，增强药物在体肠吸收能力。

Objective To construct taxifolin phospholipid complex albumin nanoparticles (Tax-PC/BSA NPs) and optimize its preparation technology, and investigate its intestinal absorption characteristics. Methods Tax-PC/BSA NPs were prepared by solvent evaporation method and nanoparticle-albumin bound technology (Nab^TM). Box-Behnken design-response surface method (BBD-RSM) was used to optimize the preparation process and verify it. Tax-PC/BSA NPs were characterized by transmission electron microscope (TEM), particle size, polydispersity index (PDI), ζ potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) to determine the physicochemical properties and to investigate the stability of the formulation. The absorption characteristics of Tax-PC/BSA NPs were investigated to investigate the release rule of the preparation in human digestive environment. The intestinal absorption characteristics of Tax-PC/BSA NPs were evaluated in rats with unidirectional intestinal perfusion model in situ. Results The optimal preparation process of Tax-PC/BSA NPs included drug-phosphorus ratio of 1:3, drug/BSA ratio of 1:9.39, oil-water ratio of 1:11.51, and sonication time of 7.76 min. Results of three validation experiments showed that the encapsulation efficiency of Tax-PC/BSA NPs was (86.14 ±0.38)%, the drug loading was (7.27 ±0.03)%, and the leakage rate was (0.87 ±0.04)%. The Tax-PC/BSA NPs prepared by the optimal process were spherical, the average particle size was (184.90 ±0.98) nm, the PDI was 0.275 ±0.010, and the ζ potential was (−36.60 ±0.53) mV. The formation of Tax-PC/BSA NPs was further verified by DSC, FT-IR, and XRD. The solubility of Tax-PC/BSA NPs increased 38.48 times compared with Tax, lgP > 1, and lipid solubility was significantly improved; Tax-PC/BSA NPs lyophilized powder was stable at 4℃ for 3 months. The cumulative release rates of Tax, Tax-PC, and Tax-PC/BSA NPs were (48.26 ±0.71)%, (71.86 ±1.83)%, (82.73±0.62)%, respectively. Tax-PC/BSA NPs, Tax-PC and Tax were absorbed in all intestinal segments, and the main absorption sites were duodenum and jejunum, and the absorption rate constants and apparent absorption coefficients of Tax-PC/BSA NPs were significantly higher than those of Tax-PC and Tax (P < 0.05, 0.01). Conclusion The optimized preparation technology of Tax-PC/BSA NPs is stable and feasible; prepared Tax-PC/BSA NPs effectively improved the liposolubility and water-solubility of the drug, and enhanced the absorption of the drug in the body intestine.

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吉林省科技发展计划项目（YDZJ202201ZYTS628）；长春中医药大学研究生精品示范课程建设创新示范项目（2022JP06）