不同疏水核心聚合物胶束与其载药性能的相关性研究  

Correlation Study of Different Hydrophobic Core Polymer Micelles and Their Drug Delivery Properties

作　　者：况文亮 丁权 周志炜 郭子璐 王上点 朱卫丰[1] 吴文婷 KUANG Wenliang;DING Quan;ZHOU Zhiwei;GUO Zilu;WANG Shangdian;ZHU Weifeng;WU Wenting(Institute of Modern Chinese Medicine Pharmaceutical Industry,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制药产业学院,南昌330004

出　　处：《中国药学杂志》2023年第21期1931-1939,共9页Chinese Pharmaceutical Journal

基　　金：江西省自然科学基金青年项目资助(20212BAB216013);江西省教育厅科学技术研究项目资助(GJJ211232);江西中医药大学校级科技创新团队项目资助(CTXD22006);江西中医药大学博士科研启动基金项目资助(2021WBZR006)。

摘　　要：目的 探究不同疏水内核的聚合物胶束(polymeric micelles, PM)的载药规律。方法 选用Pluronic家族中4种亲水亲油平衡值不同的F127、F108、L64、P123为载体材料,以疏水程度不同的葛根素(puerarin, PUE,LogP=0.41)及大豆苷元(daidzein, DE, LogP=2.28)为模型药物,采用薄膜水化法制备4种空白PM及8种负载PUE或DE的载药PM,并通过纳米粒度仪与透射电子显微镜进行形貌表征,芘荧光探针测定PM内核的疏水性强弱,跟踪载药粒径随时间变化分析PM自身结构稳定性,核磁共振氢谱(1HNMR)分析药物在PM中的空间分布,阐明上述性质与PM的增溶效果、载药稳定性及体外释放等载药性能之间的关联。结果 成功制备了4种空白PM(F127/PM、F108/PM、L64/PM、P123/PM)和8种相应的载药PM,粒径均一且小于50 nm,呈类球形,形成的疏水内核的疏水性强弱为P123>L64>F127>F108。并发现,PM对于PUE与DE的增溶能力主要取决于药物与载体的相容性,即二者的疏水性差异;PM的载药稳定性以及体外释放均同时受到药物与载体之间的相容性和PM自身结构稳定性的影响。结论 PM结构稳定性、药物在PM中的空间分布、药物与PM的相容性均是影响PM载药性能的关键因素,这可为PM的设计开发提供理论基础。OBJECTIVE To investigate the drug loading behaviour of polymeric micelles with different hydrophobic cores.METHODS In this study,F127,F108,L64 and P123 with different hydrophilic and hydrophilic balance values in Pluronic family were selected as carrier materials.Puerarin(PUE,LogP=0.41)and daidzein(DE,LogP=2.28)with different degrees of hydrophobicity were used as model drugs.Four blank PMs and eight drug-loaded PMs were prepared by thin-film hydration,and characterized by nanometer particle size tester and transmission electron microscopy.And the hydrophobicity of PM cores was determined by pyrene fluorescence probe.The structural stability of PMs was also analyzed based on the change of drug-loaded particle size over time.Moreover,nuclear magnetic resonance hydrogen spectroscopy was applied to observe the spatial distribution of drugs in PM.Accordingly,the correlation between the above properties and the solubilization effect,drug delivery stability and in vitro release of PM was elucidated.RESULTS Four blank PMs and eight corresponding drug-loaded PMs with uniform particle size(<50 nm)and sphere-like shape were successfully prepared,and the hydrophobic strength of the formed hydrophobic core was P123>L64>F127>F108.The RESULTS show that the solubilization ability of PM for PUE and DE depends mainly on the compatibility of drug and carrier,namely their hydrophobicity difference,while the drug-loading stability and in vitro release of PM are both affected by the compatibility between drug and carrier and the structure stability of PM.CONCLUSION It can be concluded that the PM's structure stability,the spatial distribution of drug within PM and the compatibility between drug and PM all affect the drug delivery performance of PM,which can provide a theoretical basis for the design and development of PM.

关 键 词：聚合物胶束 疏水核心 载药规律 空间分布 相容性 稳定性 

分 类 号：R944[医药卫生—药剂学]