酪蛋白胶束与氟雷拉纳相互作用及其复合物性质研究  

Study on the interaction between micellar casein and fluralaner,and the properties of their complexes

作　　者：王晓兵 杨敏[1] 吴昊 WANG Xiaobing;YANG Min;WU Hao(College of Sciences,Gansu Agricultural University,Lanzhou 730070,China)

机构地区：[1]甘肃农业大学理学院,甘肃兰州730070

出　　处：《南京农业大学学报》2025年第2期436-445,共10页Journal of Nanjing Agricultural University

基　　金：国家自然科学基金项目(32360597);甘肃省重点研发计划项目(23YFNA0017);甘肃省自然科学基金项目(22JR5RA861)。

摘　　要：[目的]为了开发氟雷拉纳(fluralaner, FLU)新剂型,以酪蛋白胶束(micellar casein, MC)为载体研制了MC-FLU粉末制剂并研究其特性。[方法]采用pH驱动法制备了MC-FLU自组装复合物,并分别在pH10.0和pH7.0条件下制备了MC-FLU的碱性和中性复合物,分析了不同复合物中MC与FLU的作用机制;经冷冻干燥和喷雾干燥制得MC-FLU复合物粉末,采用扫描电镜(SEM)等方法表征了复合物结构,测定了复合物的溶解性,并评价了复合物的模拟胃肠消化特性。[结果]3种pH值(5.2、7.0、10.0)下MC与FLU相互作用的热力学参数ΔG<0、ΔH<0、ΔS<0,二者主要作用为氢键和范德华力,且结合过程为自发过程。298 K下,自组装复合物中FLU与MC的结合常数为2.25×10^(6) L·mol^(-1),中性复合物中二者结合常数为2.12×10^(5) L·mol^(-1),碱性复合物中结合常数为2.26×10^(4) L·mol^(-1)。中性复合物粒径约为200 nm,碱性复合物粒径约为120 nm,自组装复合物粒径随着FLU添加量的增加而显著增大。3种pH值条件下复合物的Zeta-电位均小于零。用SEM观察发现,喷雾干燥法制得的中性复合物粒径最小。冷冻干燥法制得的复合物溶解性高于喷雾干燥样品。模拟胃肠消化试验结果表明,经MC负载后,FLU的累积释放率显著降低。[结论]MC对FLU具有较高的亲和性,可作为载体对其进行负载,进而改善FLU的溶解性,且对其具有缓释作用。研究结果可为FLU新载体的开发及MC在药物分子负载中的应用提供参考依据。[Objectives]In order to develop the new formulation of fluralaner(FLU),micellar casein(MC)was chosen as the matrix to prepare MC-FLU complexes powder,which preperties were studied.[Methods]The self-assembled complex of MC-FLU was prepared by pH-shifting method,and the complexes of MC-FLU were prepared at both pH10.0 and pH7.0 labeled as alkaline complex and neutral complex,respectively.The interactions between MC and FLU in different complexes were analyzed.The MC-FLU complexes were prepared by freeze drying and spray drying,and the structures of them were characterized by scanning electron microscopy(SEM).The solubilities of the complexes were also determined,as well as their release profile of FLU during simulated gastrointestinal digestion.[Results]The thermodynamic parameters of the binding processes for MC and FLU at different pH values(5.2,7.0,10.0)were ofΔG<0,ΔH<0 andΔS<0.The main interaction between MC and FLU was hydrogen bonds and van der Waals forces,and the binding processes were spontaneous.The binding constant of MC and FLU in self-assembled complexes at 298 K was 2.25×10^(6) L•mol^(-1),but 2.12×10^(5) L•mol^(-1) for neutral complexes,and 2.26×10^(4) L•mol^(-1) for alkaline complexes.The size of neutral complexes was about 200 nm,but 120 nm for alkaline complexes.However,the size of self-assembled complexes increased with the increasing in FLU content.In addition,the Zeta-potential of MC-FLU complexes at different pH values were all negative.SEM results showed that the spray-dried neutral complexes had smaller size than those of alkaline complexes and self-assembled complexes.The main interaction between MC and FLU at different pH values among them,the binding constant of MC and FLU was the largest for self-assembled complexes.The solubility of freeze-dried complexes was higher than those of spray-dried complexes.The result of simulated gastrointestinal digestion showed that the cumulative release rate of FLU decreased significantly after MC loading.[Conclusions]MC had high affinity for

关 键 词：酪蛋白胶束 氟雷拉纳 自组装技术 相互作用 复合物 

分 类 号：TS252.9[轻工技术与工程—农产品加工及贮藏工程]