目的 探究固体脂质纳米粒和微胶囊2种制剂方法对姜黄素理化表征的影响，并对其在SD大鼠体内的药动学行为进行定性定量研究。方法 分别采用薄膜-超声分散法和均质乳化-喷雾干燥法制备姜黄素固体脂质纳米粒（curcumin solid lipid nanoparticles，Cur-SLN）和姜黄素微胶囊（curcumin microcapsules，Cur-MC），并对其外观形态、粒度分布、ζ电位、包封率、载药量和体外释放度进行表征；通过超高效液相色谱串联飞行时间质谱（UPLC-QTOF-ESI-MS/MS）法鉴定ig后大鼠血浆中的代谢产物，采用超高效液相色谱串联三重四级杆质谱（UPLC-ESI-MS/MS）法测定血药浓度，比较药动学参数和生物利用度。结果 2种制剂方法均可显著降低姜黄素的粒径，使其均匀分布，Cur-SLN和Cur-MC的平均粒径分别为（184.3±7.9）、（415.3±10.3）nm，ζ电位分别为（-48.1±0.9）、（-16.4±0.4）mV，Cur-SLN和Cur-MC可将姜黄素的体外释药率从原料药的51.12%分别提高至87.79%和83.02%。ig后大鼠血浆代谢物主要为姜黄素及其葡萄糖醛酸化代谢物（curcumin glucuronide，Cur-glu），与游离姜黄素（free curcumin，Cur-F）组相比，2种水溶姜黄素制剂的药时曲线下面积（AUC_0～t）、达峰浓度（C_max）等药动学参数显著提高，Cur-SLN组姜黄素和Cur-glu的相对生物利用度分别增加4.31和4.63倍，Cur-MC组分别增加3.19和2.73倍。结论 2种制剂均可显著提高姜黄素的口服吸收生物利用度，且固体脂质纳米粒优于微胶囊。

Objective To investigate the effect of solid lipid nanoparticles and microcapsules on the characterization of curcumin, and qualitatively and quantitatively study their pharmacokinetics in SD rats.Methods Curcumin solid lipid nanoparticles (Cur-SLN) and curcumin microcapsules (Cur-MC) were prepared by film-ultrasonic dispersion method and homogenization emulsification-spray drying method, respectively. And then their appearance morphology, particle size distribution, ζ potential, entrapment efficiency, drug-loading capacity and in vitro release were characterized. The metabolites in the plasma of SD rats were identified by ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry (UPLC-QTOF-ESI-MS/MS). And then the plasma concentration was determined by ultra-high performance liquid chromatography-tandem triple quadruple rod mass spectrometry (UPLC-ESI-MS/MS) to compare pharmacokinetic parameters and bioavailability. Results Both methods can significantly reduce the particle size of curcumin and make it evenly distributed. The mean particle size of Cur-SLN and the Cur-MC respectively were (184.3 ±7.9) and (415.3 ±10.3) nm, and the ζ potential were (-48.1 ±0.9) and (-16.4 ±0.4) mV, respectively. Cur-SLN and Cur-MC can increase the in vitro release rate of curcumin from 51.12% of suspension to 87.79% and 83.02%. The plasma metabolites of rats after ig are mainly curcumin and curcumin glucuronide (Cur-glu). Compared to free curcumin (Cur-F) group, the pharmacokinetic parameters of area under curve (AUC_0—t) and maximum concentration (C_max) of experimental group were significantly improved. And the relative bioavailability of curcumin and Cur-glu of Cur-SLN was increased by 4.31 and 4.63 times, and that of Cur-MC was increased by 3.19 and 2.73 times, respectively. Conclusion Both formulations can observably enhance the oral absorption bioavailability of curcumin, and Cur-SLN is superior to Cur-MC.

R283.6

国家自然科学基金项目（82073994）；四川省科技厅科技项目（2020JDJQ0049）