载白藜芦醇的氨基修饰介孔二氧化硅纳米粒的制备及体内体外评价  

Preparation and Evaluation of Resveratrol-loaded Mesoporous Silica Nanoparticles Modified by Amino

作　　者：张蓉蓉[1] 王国伟[1] 徐骏军 屠钰 杨亚冬[3] 李范珠[1] 

机构地区：[1]浙江中医药大学药学院,杭州310053 [2]浙江中医药大学实验动物研究中心,杭州310053 [3]浙江省医学科学院生物工程所,杭州310013

出　　处：《中国药学杂志》2015年第5期413-419,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81274089;81473361);浙江省自然科学基金资助项目(LZ13H280001);浙江省大学生科技创新活动计划项目(2013R410059)

摘　　要：目的本实验拟制备载白藜芦醇的氨基修饰介孔二氧化硅纳米粒(NH2-MSN-RES),以期提高白藜芦醇(Res)的生物利用度。方法采用改良的Stober法合成氨基修饰介孔二氧化硅(NH2-MSN),发明了反复饱和溶液吸附法载入白藜芦醇制备载白藜芦醇的氨基修饰介孔二氧化硅纳米粒,透析袋法考察其体外释药特性,MTT法考察载体对Caco-2的细胞毒性,研究载体对白藜芦醇的跨膜转运能力和在大鼠体内的药动学特性。结果氨基修饰介孔二氧化硅氨基成功修饰,呈圆整球形,分布均一,对Caco-2细胞无明显的毒性。反复饱和溶液吸附法吸附8次,载白藜芦醇的氨基修饰介孔二氧化硅纳米粒的载药量为(19.26±2.51)%,体外释药呈现明显的缓控释特性,载白藜芦醇的氨基修饰介孔二氧化硅纳米粒对Caco-2细胞单层模型具有良好的跨膜转运能力。药动学参数表明,载白藜芦醇的氨基修饰介孔二氧化硅纳米粒的AUC0-t是白藜芦醇溶液的2.58倍,并且t1/2、tmax和ρmax显著提高,同时载体使白藜芦醇由单室模型变为二室模型。结论改良的Stober法成功合成氨基修饰介孔二氧化硅,反复饱和溶液吸附法能够有效提高载药量,载白藜芦醇的氨基修饰介孔二氧化硅纳米粒提高了白藜芦醇的生物利用度,氨基修饰介孔二氧化硅是一种有前景的口服给药纳米材料。OBJECTIVE To prepare and evaluate resveratrol-loaded mesoporous silica nanoparticles modified by amino （NH2- MSN-RES） to improve the bioavailability of resveratrol. METHODS Mesoporous silica nanopartieles modified by amino （NH2- MSN） were synthesized by the modified Stober method. The structure of the nanoparticles were analyzed and characterized by FT-IR, Malvern particle size analyzer, and TEM. By introducing the innovative preparation process of repeated saturated solution adsorbing method, RES was encapsulated into NH2-MSN in larger amount. Dialysis bag method was used to investigate the in vitro drug release characteristics and MTT method was used to investigate the cytotoxicity on Caeo-2 cells. The transport ability of the carrier was investi- gated by the Caco-2 cells monolayer model. Finally, the pharmacokineties of NH2-MSN-RES was studied in rats. RESULTS The particle size distribution of NH2-MSN was uniform with an average value of （ 98.4 ± 2. 8 ）nm, and the Zeta potential was （ 13.2 ± 1.8 ） mv. Within the scope of 0 -20μg · mL-1 , NH2-MSN had no obvious toxicity on Caco-2 cells. After 8 times of repeated adsorp- tion, the drug loading of NH2-MSN-RES reached up to （ 19.26± 2. 51 ） %. In the drug release experiment, the cumulative release quantity of NH2-MSN-RES was 73.3% within 48 h, indicating sustained-release characteristics. NH2-MSN-RES had good ability of transmembrane transport in the Caeo-2 cell monolayer model, and the two-way apparent permeability coefficient （ P,pp ） was much larger than the RES solution. In the pharmaeokinetic study, RES solution complied with one-compartment model, whereas NH2-MSN-RES complied with two-compartment model, indicating that the carrier changed the pharrnacokinetic characteristics of RES. The AUC0_t of NH2-MSN-RES was 2. 58-fold of that of RES solution, what＇s more, the tl/2 , t and Pm~ of NH2-MSN-RES were significantly greater than those of RES solution. CONCLUSION NH2-MSN is synthesized by modified Stober method successfully. Repe

关 键 词：白藜芦醇 介孔二氧化硅 氨基修饰 反复饱和溶液吸附法 口服 体内体外评价 

分 类 号：R944[医药卫生—药剂学]