目的 制备甘草多糖稳定的黄芩苷纳米晶（Glycyrrhiza polysaccharide-stabilized baicalin nanocrystals，Bai-NCs/GP），并考察其理化性质及体内药动学。方法 采用介质研磨法制备Bai-NCs/GP，以平均粒径和多分散性指数（polydispersity index，PDI）为考察指标，单因素实验优化处方和工艺；对优化所得的Bai-NCs/GP进行形态、晶型、溶解度与溶出度表征，LC-MS/MS法测定大鼠分别ig给予Bai-NCs/GP与黄芩苷后的血药浓度，对比其生物利用度差异。结果 Bai-NCs/GP的最佳处方和工艺参数为黄芩苷与甘草多糖质量比为10∶5，黄芩苷的用量为1.00%，研磨转速为1 400 r/min，研磨时间为24 h。Bai-NCs/GP呈不规则纳米颗粒，平均粒径为（146.29±8.07）nm，多分散指数（polydispersity index，PDI）为0.22±0.01，ζ电位为（-21.60±0.58）mV。与黄芩苷原料药相比，Bai-NCs/GP的结晶度降低，溶解度增加了43倍，溶出度显著改善；Bai-NCs/GP的达峰浓度（maximum plasma concentration，C_max）和药-时曲线下面积（area under the plasma concentration-time curve，AUC_0～t）分别为（2 318.65±341.60）ng/mL和（34 439.68±5 548.79）ng·h/mL，是黄芩苷的2.31倍和2.77倍，口服生物利用度显著提高。结论 甘草多糖可以作为稳定剂用于制备黄芩苷纳米晶，所制备的Bai-NCs/GP能够提高黄芩苷的溶解度和体外溶出度，改善黄芩苷的口服生物利用度。

Objective To prepare Glycyrrhiza polysaccharide-stabilized baicalin nanocrystals (Bai-NCs/GP) and investigate their physicochemical properties and in vivo pharmacokinetics. Methods Bai-NCs/GP were prepared using a media milling method. The formulation and process were optimized through single-factor experiments based on average particle size and polydispersity index (PDI). The optimized Bai-NCs/GP formulation was characterized for morphology, crystal form, solubility, and dissolution rate. LC-MS/MS was used to measure blood concentrations of Bai-NCs/GP and baicalin after oral administration in rats, comparing their bioavailability differences. Results The optimal formulation and processing parameters for Bai-NCs/GP were determined as follows: a baicalin to Glycyrrhiza polysaccharide ratio of 10:5, a baicalin content of 1.00%, a grinding speed of 1 400 r/min, and a grinding time of 24 h. Bai-NCs/GP exhibited irregular nanoparticles with an average particle size of (146.29 ± 8.07) nm, polydispersity index (PDI) of 0.22 ± 0.01, and ζ potential of (-21.60 ± 0.58) mV. Compared to baicalin, Bai-NCs/GP showed reduced crystallinity, 43- fold increased solubility, and significantly improved dissolution rate. The peak concentration (C_max) and AUC_0—t of Bai-NCs/GP were (2 318.65 ± 341.60) ng/mL and (34 439.68 ± 5 548.79) ng·h/mL, respectively, representing 2.31-fold and 2.77-fold increases over baicalin, with markedly enhanced oral bioavailability. Conclusion Glycyrrhiza polysaccharide can serve as a stabilizer in the preparation of baicalin nanocrystals. The resulting Bai-NCs/GP nanocrystals enhance the solubility and in vitro dissolution rate of baicalin, thereby improving its oral bioavailability.

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国家自然科学基金项目（82460852）；国家自然科学基金项目（82260848）；江西省自然科学基金项目（20232BAB216139）；国家青年岐黄学者培养项目（2022256）；江西中医药大学校级科技创新团队发展计划项目（CXTD22006）