黄芩苷-甘草蛋白纳米粒的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics study of baicalin encapsulated glycyrrhizaprotein nanoparticles

作　　者：章丹 阮清锋 熊鑫[1] 程璐[1] ZHANG Dan;RUAN Qingfeng;XIONG Xin;CHENG Lu(Department of Pharmacy,First Municipal Hospital,Hubei Wuhan 430033,China)

机构地区：[1]武汉市第一医院药学部,湖北武汉400033

出　　处：《中国医院药学杂志》2024年第18期2095-2100,2114,共7页Chinese Journal of Hospital Pharmacy

基　　金：武汉市卫生健康委员会面上重点项目(编号:WZ20A10);武汉市科技局知识创新专项曙光计划项目(编号:2023020201020531)。

摘　　要：目的:制备黄芩苷-甘草蛋白纳米粒(baicalin encapsulated glycyrrhiza protein nanoparticles,b-GP NP),并考察其体内药动学。方法:pH-凝聚法制备b-GP NP,以黄芩苷用量、甘草蛋白用量以及pH值为影响因素,药物包封率和纳米粒的粒径大小为评价指标,通过Box-Behnken响应面法优化制备方案。测定纳米粒形貌、药物包封率、载药量、粒度分布、多分散性等。并对b-GP NP的体内药动学进行研究,将黄芩苷对照品和b-GP NP分别灌胃至大鼠体内,通过高效液相色谱串联质谱法(HPLC-MS)测定不同时间点大鼠体内黄芩苷的血药浓度。结果:最优处方制备的b-GP NP呈球状,粒径为212.3 nm,大小均一,具有良好的分散性,载药量和包封率分别达到9.1%和81.8%。b-GP NP和黄芩苷对照品在大鼠体内均符合药动学二室模型,且相比于黄芩苷对照品,纳米粒Cmax、AUC0-t显著升高,CL降低(P<0.01),口服生物利用度增加至2.36倍。结论:甘草蛋白纳米粒制备工艺简单,载药量高,可提高黄芩苷成药性和口服吸收效率。OBJECTIVE To prepare baicalin encapsulated glycyrrhiza protein nanoparticles and explore their in vivo pharmacokinetics.METHODS Baicalin encapsulated glycyrrhiza protein nanoparticles were prepared by pH-agglomeration method.Taking the dosage of baicalin and glycyrrhiza protein,as well as pH value as influencing factors,encapsulation efficiency of baicalin and size of nanoparticle as evaluation parameters,the preparation of baicalin encapsulated glycyrrhiza protein nanoparticles was optimized with Box-Behnken design.After optimization,morphology,encapsulation efficiency,drug loading,particle size distribution and polydispersity of nanoparticles were determined.Then in vivo pharmacokinetics of baicalin encapsulated glycyrrhiza protein nanoparticles were examined.Briefly,free baicalin and nanoparticles were given to rats orally and the plasma concentrations of baicalin in rats at different timepoints were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS).RESULTS The baicalin encapsulated glycyrrhiza protein nanoparticles prepared by the optimal prescription were spherical with a particle size of 212.3 nm.The nanoparticles were uniform with an excellent dispersibility and drug loading capacity and encapsulation efficiency were 9.1%and 81.8%respectively.For in vivo pharmacokinetics studies,both nanoparticles and free baicalin conformed to the pharmacokinetic two-chamber model in rats.As compared with free baicalin,Cmax and AUC0-t of nanoparticles rose obviously.CL declined(P<0.01)and oral bioavailability spiked to 2.36 folds.CONCLUSION The preparation process of glycyrrhiza protein nanoparticles is simple with a high drug loading capacity.As a novel drug delivery system,it improves oral absorption efficiency of baicalin.

关 键 词：黄芩苷 甘草蛋白纳米粒 pH-凝聚法 体内药动学 

分 类 号：R944.9[医药卫生—药剂学]