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

 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AUC_0-t是白藜芦醇溶液的2.58倍,并且t_1/2、t_max和ρ_max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。

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

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 nanoparticles 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 Caco-2 cells. The transport ability of the carrier was investigated by the Caco-2 cells monolayer model. Finally, the pharmacokinetics 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 0-20 μg·mL^-1, NH₂-MSN had no obvious toxicity on Caco-2 cells. After 8 times of repeated adsorption, 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 Caco-2 cell monolayer model, and the two-way apparent permeability coefficient (P_app) was much larger than the RES solution. In the pharmacokinetic study, RES solution complied with one-compartment model, whereas NH₂-MSN-RES complied with two-compartment model, indicating that the carrier changed the pharmacokinetic characteristics of RES. The AUC_0-t of NH₂-MSN-RES was 2.58-fold of that of RES solution, what′s more, the t_1/2, t_max, and ρ_max of NH₂-MSN-RES were significantly greater than those of RES solution. CONCLUSION NH₂-MSN is synthesized by modified Stober method successfully. Repeated saturated solution adsorbing method could effectively improve the drug loading. NH₂-MSN-RES improves the bioavailability of RES prominently. NH₂-MSN will be a promising nano-material for oral drug delivery carrier.