不同稳定剂修饰的槲皮素纳米晶在大鼠体内注射药动学及组织分布研究  

Pharmacokinetics and tissue distribution of quercetin nanocrystals modified with different stabilizers following intravenous delivery in rats

作　　者：胡菲 车智慧 王哲 李方琴 闫巧 沈成英 申宝德 袁海龙 HU Fei;CHE Zhi-hui;WANG Zhe;LI Fang-qin;YAN Qiao;SHEN Cheng-ying;SHEN Bao-de;YUAN Hai-long(Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Department of Pharmacy,Air Force Medical Center,PLA,Beijing 100142,China;Department of Pharmacy,Jiangxi Provincial People’s Hospital,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]空军特色医学中心药学部,北京100142 [3]江西省人民医院药学部,江西南昌330004

出　　处：《中草药》2022年第9期2697-2705,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81803741);国家自然科学基金资助项目(81873092);江西中医药大学博士科研启动基金资助项目(2021BSZR025)。

摘　　要：目的以普朗尼克F68(F68)、普朗尼克F127(F127)、甘草酸(glycyrrhizinic acid,GL)、维生素E聚乙二醇琥珀酸酯(TPGS)为稳定剂制备槲皮素纳米晶(quercetin nanocrystals,QT-NCs),探讨不同稳定剂种类对QT-NCs注射药动学及组织分布的影响。方法采用HPLC法测定大鼠血浆和组织中的槲皮素质量浓度,并用DAS 2.0软件计算其药动学参数,进行比较。结果药动学结果显示,AUC0~t呈如下顺序:QT-NCs/GL[(464.87±100.51)mg·L/h]>QT-NCs/TPGS[(339.82±73.82)mg·L/h]>QT-NCs/F68[(293.00±44.72)mg·L/h]>QT-NCs/F127[(245.01±28.72)mg·L/h]。组织分布研究结果显示,不同稳定剂修饰的QT-NCs具有不同的组织分布行为,肝脏的AUC0~t顺序与血浆AUC0~t一致。此外,QT-NCs/GL在肝、脾、肺的分布最高(P<0.01)。结论稳定剂种类可以影响QT-NCs的注射药动学及组织分布。Objective To prepare quercetin nanocrystals(QT-NCs) with pluronic F68(F68),pluronic F127(F127),glycyrrhizic acid(GL),vitamin E polyethylene glycol succinate(TPGS) as stabilizers and explore the effects of stabilizers on pharmacokinetics and tissue distribution following intravenous delivery.Methods High performance liquid chromatography(HPLC) was used to determine the concentration of quercetin in plasma and tissues of rats,and DAS 2.0 software was used to calculate its pharmacokinetic parameters for comparison.Results The pharmacokinetic results showed that AUC0~t of QT-NCs was in the following order:QT-NCs/GL [(464.87 ± 100.51) mg·L/h] > QT-NCs/TPGS [(339.82 ± 73.82) mg·L/h] > QT-NCs/F68 [293.00 ± 44.72] mg·L/h] > QT-NCs/F127[(245.01 ± 28.72) mg·L/h).AUC0~t of QT-NCs in liver showed similar order to that of plasma.Furthermore,the distribution of QTNCs/GL in liver,spleen and lung were the highest(P < 0.01).Conclusion The stabilizers’ types can influence the pharmacokinetics and tissue distribution of QT-NCs following intravenous delivery.

关 键 词：槲皮素 纳米晶 稳定剂 药动学 组织分布 

分 类 号：R285.61[医药卫生—中药学]