介孔二氧化硅载体对蛋白药物载药释药及提高酶降解稳定性的初步研究  

Preliminary study on drug load,release and protective effects of mesoporous silica carrier on proteins

作　　者：栾嘉瑶 高亦鲲 王梦洋 刘迎春[1] LUAN Jiayao;GAO Yikun;WANG Mengyang;LIU Yingchun(School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China;School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China;School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China)

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]沈阳药科大学医疗器械学院,辽宁沈阳110016 [3]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2018年第4期259-264,共6页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81503022);辽宁省科技厅博士启动基金项目(201601148)

摘　　要：目的根据模型蛋白的空间尺寸设计介孔二氧化硅载体,初步探索不同孔径载体对蛋白药物载药、释药及稳定性的保护作用。方法以表面活性剂P123为胶束模板,以正硅酸乙酯为硅源,制备介孔二氧化硅,利用透射电镜、氮气吸附-脱附等手段表征载体;以溶菌酶(lysozyme,LYS)和牛血清白蛋白(bovine serum albumin,BSA)为模型蛋白,采用SDS-PAGE电泳分析测定不同孔径载体对LYS和BSA酶降解的保护程度。结果制备出三种孔径(7、17、22 nm)介孔二氧化硅载体,三种载体对LYS和BSA的载药量均为40%左右,LYS和BSA在三种载体中的总释放度均随孔径的减小而减小,7 nm和17 nm载体分别对LYS和BSA的保护作用最强。结论介孔二氧化硅可用于高效装载蛋白药物并提高其稳定性,载体孔径尺寸越接近蛋白药物的大小,对其保护作用越强。Objective To design mesoporous silica w ith different pore size based on the size of protein aiming and to study the drug load and release as w ell as the protective effects against enzymolysis on protein drugs.Methods The surfactant P123 w as used as micellar template and tetraethoxysilane as silicon source to prepare mesoporous silica. Lysozyme and bovine serum albumin w as chosen as model drugs,protein w as loaded by adsorption equilibrium method. Transmission electron microscopy and nitrogen adsorption-desorption w as adopted to characterize the carriers. The protective effect of the carriers w ith different pore size on protein drugs against enzymolysis w as analyzed by SDS-PAGE electrophoresis. Results M esoporous silica carriers w ith pore size of 7 nm,17 nm and 22 nm w as successfully prepared. Drug load w as measured to be about40%. The efficiency of drug load and release as w ell as the cumulative release decreased w ith the decreae of spore size. Carriers w ith pore size of 7 nm and 17 nm had the best protective effects for lysozyme and bovine serum albumin,respectively. Conclusions M esoporous silica can be used for efficiently loading protein drugs and improving its stability. The more suitable the pore size of carrier for the size of protein,the stronger the protective effect it w ill have.

关 键 词：介孔二氧化硅 溶菌酶 牛血清白蛋白 稳定性 

分 类 号：R94[医药卫生—药剂学]