葛根素壳聚糖/海藻酸钠口服纳米粒的制备、表征与药动学研究  

Preparation,characterization and pharmacokinetics of puerarin chitosan/sodium alginate oral nanoparticles

作　　者：李娜[1] 颜洁 关志宇[1] 朱卫丰[1] 钟凌云[1] 周冬艳 LI Na;YAN Jie;GUAN Zhi-yu;ZHU Wei-feng;ZHONG Ling-yun;ZHOU Dong-yan(School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nangchang 330004,China)

机构地区：[1]江西中医药大学药学院,江西南昌330004

出　　处：《中草药》2020年第15期3894-3900,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重点研发计划中医药现代化研究重点专项(2017YFC1702904);国家重点研发计划中医药现代化研究重点专项(2018ZX09721002);江西省教育厅科技计划项目(GJJ170718);中药学一流学科科研项目(JXSYLXK-ZHYAO049)。

摘　　要：目的制备及表征葛根素壳聚糖/海藻酸钠口服纳米粒(Pur-CS/SA-NPs),并进行药动学研究。方法采用自组装法制备Pur-CS/SA-NPs,对Pur-CS/SA-NPs混悬液和冻干粉的形态、粒径、多分散指数(PDI)、Zeta电位、包封率、载药量、微观结构等进行表征;建立葛根素LC-MS/MS分析方法,测定大鼠口服给予Pur-CS/SA-NPs后血浆中葛根素的浓度,考察其药动学特征。结果Pur-CS/SA-NPs混悬液和冻干粉的形态结构完整,其中Pur-CS/SA-NPs混悬液的粒径为(208.327±1.870)nm,PDI为0.131±0.006,包封率为(89.056±1.680)%,载药量为(44.528±0.840)%,Pur-CS/SA-NPs冻干粉的粒径为(260.000±0.475)nm,Zeta电位为(47.300±0.208)mV,包封率为(86.234±0.873)%,载药量为(43.117±0.234)%,无新化学键和晶体形成;Pur-CS/SA-NPs的药时曲线下面积(AUC0~24和AUC0~∞)、达峰时间(tmax)、达峰浓度(Cmax)分别为(833.067±132.546)mg·h/L、(844.919±154.768)mg·h/L、(1.000±0.098)h、(236.318±36.864)mg/L,葛根素的AUC0~24、AUC0~∞、tmax、Cmax分别为(250.087±32.156)mg·h/L、(250.091±28.398)mg·h/L、(0.500±0.031)h、(191.830±17.963)mg/L,Pur-CS/SA-NPs的AUC0~24、AUC0~∞、tmax、Cmax分别为葛根素的3.331、3.378、2.000、1.232倍。结论自组装法制备的Pur-CS/SA-NPs形态结构稳定,口服给药后药物在体内的AUC0~24、AUC0~∞、tmax均显著增大,循环时间也相对延长,显著提高了葛根素的生物利用度。Objective To prepare and characterize puerarin chitosan/sodium alginate oral nanoparticles(Pur-CS/SA-NPs)and conduct its pharmacokinetics studies.Methods Pur-CS/SA-NPs were prepared by self-assembly method,the morphology,particle size,polydispersity index(PDI),zeta potential,entrapment efficiency,drug loading and microstructure of Pur-CS/SA-NPs suspension and lyophilized powder were characterized.To determine the concentration of puerarin in plasma after oral administration of nanoparticles to rats,an LC-MS/MS analysis method for puerarin was established,and its pharmacokinetic characteristics were investigated.Results The morphology,structure and texture of Pur-CS/SA-NPs suspension and lyophilized powder were complete and fine,no new chemical bonds and crystals were formed.The particle size,PDI,Zeta potential,encapsulation efficiency,and drug loading of Pur-CS/SA-NPs suspension were(208.327±1.870)nm,0.131±0.006,(89.056±1.680)%and(44.528±0.840)%,respectively.The particle size,Zeta potential,encapsulation efficiency and drug loading of Pur-CS/SA-NPs lyophilized powder were(260.000±0.475)nm,(47.300±0.208)mV,(86.234±0.873)%and(43.117±0.234)%,respectively.The AUC0—24,AUC0—∞,tmax and Cmax of Pur-CS/SANPs were(833.067±132.546)mg·h/L,(844.919±154.768)mg·h/L,(1.000±0.098)h and(236.318±36.864)mg/L,respectively.The AUC0—24,AUC0—∞,tmax and Cmax of puerarin were(250.087±32.156)mg·h/L,(250.091±28.398)mg·h/L,(0.500±0.031)h and(191.830±17.963)mg/L,respectively.The AUC0—24,AUC0—∞,tmax and Cmax of Pur-CS/SA-NPs were 3.331,3.378,2.000,and 1.232 times of puerarin,respectively.Conclusion The structure of Pur-CS/SA-NPs prepared by self-assembly method is stable.After oral administration,the AUC0—24,AUC0—∞and tmax of the drug in the body are significantly increased,and the circulation time is relatively extended,which significantly improve bioavailability of puerarin.

关 键 词：葛根素 壳聚糖 海藻酸钠 口服纳米粒 表征 药动学 LC-MS/MS 冷冻干燥 包封率 载药量 药时曲线下面积 达峰时间 药峰浓度 自组装法 生物利用度 

分 类 号：R283.6[医药卫生—中药学]