目的 制备D-α-维生素E聚乙二醇1000琥珀酸酯（TPGS）修饰岩白菜素固体脂质纳米粒（TPGS surface-modified bergenin solid lipid nanoparticles，TPGS-Ber-SLN），并考察其体外释药和口服药动学行为。方法 采用高压均质法制备TPGS-Ber-SLN。以包封率、载药量和粒径为考察指标，通过单因素考察结合Box-Behnken设计-效应面法（Box Behnken design- response surface methodology，BBD-RSM）优化TPGS-Ber-SLN处方，并制备成冻干粉末。X射线粉末衍射法（X-ray powder diffraction，XRPD）和差式扫描量热法（differential scanning calorimetry，DSC）分析岩白菜素在TPGS-Ber-SLN冻干粉末中的存在状态，透析袋法考察TPGS-Ber-SLN在不同介质中释药情况。以岩白菜素原料药为参考，比较TPGS-Ber-SLN在体内药动学行为及口服生物利用度。结果 TPGS-Ber-SLN最佳处方工艺：岩白菜素用量为40 mg，单硬脂酸甘油酯用量525 mg，泊洛沙姆188质量浓度为17.5 mg/mL，TPGS质量浓度为0.2 mg/mL，均质次数为9次。TPGS-Ber-SLN的平均包封率、载药量、粒径及ζ电位分别为（83.16±1.09）%、（4.97±0.13）%、（229.46±19.07）nm和（-15.67±0.23）mV，体外释药过程符合Weibull模型。口服药动学结果显示，TPGS-Ber-SLN的t_max延长至（2.07±0.43）h，t_1/2延长至（4.21±0.78）h，C_max和生物利用度分别提高至3.91倍和5.34倍。结论 TPGS-Ber-SLN显著改变了岩白菜素的药动学行为，增加了口服吸收生物利用度。

Objective To prepare D-α-vitamin E polyethylene glycol 1000 succinate (TPGS) surface-modified bergenin (Ber) solid lipid nanoparticles (TPGS-Ber-SLN), and investigate its drug release in vitro and oral pharmacokinetics behavior. Methods High pressure homogenization method was used to prepare TPGS-Ber-SLN. Encapsulation rate, drug loading and particle size were taken as evaluation indexes, single factor investigation method combined with Box-Behnken design-response surface method was employed to optimize the prescription process of TPGS-Ber-SLN. Lyophilized powder of TPGS-Ber-SLN was also prepared. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were employed to analyze the state of Ber in lyophilized powder of TPGS-Ber-SLN. In vitro drug release behavior of TPGS-Ber-SLN in different pH media were investigated by dialysis bag method. Using Ber suspension as control, pharmacokinetics behavior in vivo of TPGS-Ber-SLN and oral bioavailability was compared. Results Optimal prescription process of TPGS-Ber-SLN was as follow: Ber dosage was 40 mg, glycerol monostearate dosage was 525 mg, poloxamer 188 mass concentrations was 17.5 mg/mL, TPGS mass concentrations was 0.2 mg/mL and homogenization times were nine times. Average envelopment efficiency, drug loading, particle size and ζ potential of TPGS-Ber-SLN were (83.16 ±1.09)%, (4.97 ±0.13)%, and (229.46 ±19.07) nm and (-15.67 ±0.23) mV, respectively. The drug release process of TPGS-Ber-SLN in vitro accorded with Weibull model. Results of oral pharmacokinetics showed that t_max of TPGS-Ber-SLN was delayed to (2.07 ±0.43) h, t_1/2 was extended to (4.21 ±0.78) h, C_max and oral bioavailability were increased to 3.91 fold and 5.34 fold, respectively. Conclusion TPGS-Ber-SLN significantly altered the pharmacokinetic behavior of Ber in vivo and increased its oral bioavailability effectively.

R283.6

上海市科委项目（21S21903400）