TPGS表面修饰岩白菜素固体脂质纳米粒的制备与口服生物利用度研究  

Formulation optimization of TPGS surface-modified bergenin solid lipid nanoparticles and oral bioavailability study

作　　者：杨金枝 崔晓鸽 郝海军 YANG Jin-zhi;CUI Xiao-ge;HAO Hai-jun(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Shanghai Institute of Traditional Chinese Medicine,Shanghai 201401,China;Shanghai Leiyunshang Pharmaceutical Co.,Ltd.,Shanghai 201401,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]上海市中药研究所,上海201401 [3]上海雷允上药业有限公司,上海201401

出　　处：《中草药》2023年第13期4144-4156,共13页Chinese Traditional and Herbal Drugs

基　　金：上海市科委项目(21S21903400)。

摘　　要：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 bergeninsolidlipidnanoparticles,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 designresponse 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)m V,体外释药过程符合Weibull模型。口服药动学结果显示,TPGS-Ber-SLN的tmax延长至(2.07±0.43)h,t1/2延长至(4.21±0.78)h,Cmax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 andζpotential 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 tmax of TPGS-Ber-SLN was delayed to(2.07±0.43)h,t1/2 was extended to(4.21±0.78)h,Cmax 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.

关 键 词：岩白菜素 固体脂质纳米粒 D-α-维生素E聚乙二醇1000琥珀酸酯 药动学 口服生物利用度 

分 类 号：R283.6[医药卫生—中药学]