姜黄素固体脂质纳米粒和微胶囊的制备、表征及体内药动学的比较研究  

Curcumin solid lipid nanoparticles and microcapsules:Comparative study on preparation,characterization and pharmacokinetics

作　　者：张心洁 廖洋样 廖婉[1] 李锐[1] ZHANG Xin-jie;LIAO Yang-yang;LIAO Wan;LI Rui(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学,西南特色中药资源国家重点实验室,药学院,四川成都611137

出　　处：《中草药》2023年第5期1386-1396,共11页Chinese Traditional and Herbal Drugs

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

摘　　要：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)m V,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,ζpotential,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 theζpotential 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.

关 键 词：姜黄素 葡萄糖醛酸化代谢物 固体脂质纳米粒 微胶囊 药动学 薄膜超声分散法 均质乳化-喷雾干燥法 超高效液相色谱串联飞行时间质谱 超高效液相色谱串联三重四级杆质谱 生物利用度 

分 类 号：R283.6[医药卫生—中药学]