口服葛根素阳离子介孔硅纳米粒的研制及体外评价  

Preparation and in vitro Evaluation of Cationic Mesoporous Silica Nanoparticles Loaded with Puerarin for Oral Administration

作　　者：张宽宽 陈丹飞 张蓉蓉[2] 肖世庚 徐骏军 

机构地区：[1]宁波市镇海区招宝山街道社区卫生服务中心,浙江宁波315200 [2]浙江中医药大学药学院,浙江杭州310053 [3]浙江大学医学院附属第二医院药剂科,浙江杭州310009

出　　处：《中国医药工业杂志》2016年第5期558-564,共7页Chinese Journal of Pharmaceuticals

基　　金：浙江省中医药科技计划项目(2016ZA130);浙江省教育厅科研项目(Y201225849)

摘　　要：采用Stober法合成了氨基修饰的阳离子介孔硅纳米粒(CMSN)。所得的CMSN呈圆整球形、介孔明显,粒径为(98.4±2.8)nm,ζ电位为(13.2±1.8)m V,在0~20mg/ml范围内对Caco-2细胞无明显的细胞毒性。以CMSN为载体,采用饱和溶液吸附法反复吸附葛根素(1)7次达到满载,载药量约为18%。在含有2%十二烷基硫酸钠的磷酸盐缓冲液(pH7.4)中,1-CMSN中1的体外释药行为符合Weibull模型(R^2=0.923 6)。Caco-2肠壁单层模型中,1-CMSN的跨膜吸收和分泌表观渗透系数P_(app)(×10^(-6) cm/s)为23.89±1.22和17.03±1.21,流出率(ER)为1.403,与1原料药有显著差异(P<0.05)。The cationic mesoporous silica nanoparticles （CMSN） were synthesized by Stober method. The average particle size and ζ potential of the prepared CMSN with spherical appearance and obvious mesoporous structure were （98.4±2.8）nm and （13.2±1.8）mV. There was no obvious cytotoxicity in vitro of CMSN in the range of 0-20 μg/ml against Caco-2 cells. By using saturated solution adsorbing method, puerarin （1） was highly encapsulated into CMSN. After repeated adsorption for 7 times, the drug loading of CMSN reached a full load of about 18 %. In pH 7.4 phosphate buffer containing 2 % sodium dodecylsulfate, the release data of 1 from the 1-CMSN was well-fitted to the Weibull equation with the correlation coefficient of 0.923 6. In Caco-2 cell monolayers, the apparent permeability coefficients, Papp（A→B〉 and Papp（B→A）, were （23.89±1.22） ×10^-6 cm/s and （17.03±1.21） ×10^-6 cm/s. The effiux ratio （ER） of 1-CMSN was 1.403, which was significantly higher than that of the bulk drug （P〈0.05）.

关 键 词：阳离子介孔硅纳米粒 葛根素 口服 体外释放 细胞毒性 跨膜转运 

分 类 号：R944.9[医药卫生—药剂学]