牡荆素白蛋白纳米粒的制备及其药动学研究  

Preparation of vitexin albumin nanoparticles and its pharmacokinetic study

作　　者：张雪 王强 潘建全 王思维 吴成圆 陈云娜 王凤玲 王雷[1,5,6] 陈卫东 ZHANG Xue;WANG Qiang;PAN Jian-quan;WANG Si-wei;WU Cheng-yuan;CHEN Yun-na;WANG Feng-ling;WANG Lei;CHEN Wei-dong(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;MOE-Key Laboratory of Molecular Biology(Brain Diseases),Anhui University of Chinese Medicine,Hefei 230012,China;Hefei Hospital Affiliated to Anhui Medical University,Hefei 230011,China;School of Pharmacy,Anhui Medical University,Hefei 230032,China;MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials,Hefei 230012,China;Anhui Province Key Laboratory of Chinese Medicinal Formula,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]安徽中医药大学分子生物学(脑病)教育部重点实验室,安徽合肥230012 [3]安徽医科大学附属合肥医院,安徽合肥230011 [4]安徽医科大学药学院,安徽合肥230032 [5]省部共建安徽道地中药材品质提升协同创新中心,安徽合肥230012 [6]中药复方安徽省重点实验室,安徽合肥230012

出　　处：《中国中药杂志》2023年第19期5205-5215,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82003849,82073923);中华中医药学会(2022—2024年度)青年人才托举工程项目(CACM-2022-QNRC2-B03)。

摘　　要：该文旨在制备牡荆素白蛋白纳米粒(VT-BSA-NPs)以改善牡荆素(vitexin,VT)水溶性差而导致的体内生物利用度低的问题。利用反溶剂结晶法制备VT微粉,对VT微粉的形貌大小和理化性质进行研究,结果显示VT微粉粒径在(187.13±7.15)nm,外貌形态近似球形,大小分布均匀;相较于VT原料药,VT微粉的化学结构并未发生变化。去溶剂化-交联固化法将VT微粉制备成VT-BSA-NPs,通过单因素考察和正交试验对制备工艺进行筛选并对最优处方的粒径、PDI、Zeta电位、EE和形态学等进行质量评价,结果显示VT-BSA-NPs的平均粒径为(124.33±0.47)nm,PDI为0.184±0.012,Zeta电位为(-48.83±2.20)mV,包封率为83.43%±0.39%,均符合制剂相关要求。形态学结果表明VT-BSA-NPs外观呈近球形,形状规整,表面无黏连。体外释放结果显示相较于VT原料药,VT-BSA-NPs的释放速率显著降低,具有良好的缓释效果。LC-MS/MS建立VT的体内分析方法学并研究VT-BSA-NPs在大鼠体内的血浆药代动力学,结果表明该分析方法的特异性良好,提取回收率均大于90%;与VT原料药和VT微粉相比,VT-BSA-NPs能够显著提高AUC、MRT和t_(1/2),有利于提高VT的生物利用度。This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility.VT micro powders were prepared by the antisolvent crystallization method,and the morphology,size,and physicochemical properties of VT micro powders were studied.The results showed that the VT micro powder had a particle size of(187.13±7.15) nm,an approximate spherical morphology,and a uniform size distribution.Compared with VT,the chemical structure of VT micro powders has not changed.VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method.The preparation process was screened by single factor test and orthogonal test,and the quality evaluation of the optimal prescription particle size,PDI,Zeta potential,EE,and morphology was performed.The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm;the PDI was 0.184±0.012;the Zeta potential was(-48.83±2.20) mV,and the encapsulation rate was 83.43%±0.39%,all of which met the formulation-related requirements.The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance,regular in shape,and without adhesion on the surface.In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT,indicating a good sustained release effect.LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats.The results showed that the specificity of the analytical method was good,and the extraction recovery was more than 90%.Compared with VT and VT micro powders,VT-BSA-NPs could significantly increase AUC,MRT,and t_(1/2),which was beneficial to improve the bioavailability of VT.

关 键 词：牡荆素 微粉 白蛋白纳米粒 质量评价 血浆药动学 

分 类 号：R285.5[医药卫生—中药学] R283.6[医药卫生—中医学]