目的 用浸渍离心法制备载不同性质的难溶性药物的介孔二氧化硅纳米粒（MSNs），探寻药物质量浓度与载药量的关系和MSNs载药机制。方法 制备空白MSNs，用透射电子显微镜（TEM）和氮气吸附-脱附解析进行表征。以水飞蓟宾、葛根素、盐酸小檗碱、姜黄素和阿魏酸为模型药物，分别固定药物溶液体积和药物质量，采用浸渍离心法载药，测定载药量，分析载药规律，并用紫杉醇、丹参酮II_A和延胡索乙素3种药物对其载药规律进行验证。对载药量较高的水飞蓟宾、葛根素和阿魏酸MSNs进行扫描电子显微镜（SEM）和差示扫描量热法（DSC）表征，分析载药机制。结果 空白MSNs粒径为（220±21）nm，比表面积为353.53 m²/g，平均孔径1.53 nm，孔容积率约为0.4 cm³/g。在药载比不变的情况下，无论是固定药物溶液体积，还是固定药物质量，载药量都与药物质量浓度呈线性关系，且与药物性质无关，5种药物的综合回归方程分别为固定药物溶液体积Y＝0.351 7 X＋0.982 5，r＝0.991 4和固定药物质量Y＝0.359 2 X＋0.248 3，r＝0.991 0。SEM显示载药MSNs表面没有明显的药物结晶。载药MSNs的DSC均观察到了药物的熔融峰，但单位吸热量均比等比例的机械混合物明显减小。结论 药物溶液质量浓度是决定MSNs浸渍离心法载药效果的关键因素，药物主要以无定形及微晶形式分散于MSNs的介孔中。

Objective To investigate the relationship between drug concentration and drug loading efficiency and to explore mechanism of drug loading by incorporating different insoluble drugs into mesoporous silica nanoparticles with dipping centrifugation method. Methods Mesoporous silica nanoparticles were characterized by transmission electron microscopy and nitrogen adsorption-desorption analysis. Silybin, puerarin, berberine, curcumin, and ferulic acid were used as model drugs and loaded into mesoporous silica nanoparticles using two technologies: The volume of drug solution or drug amount was fixed respectively. The relationship between drug concentration and drug loading was analyzed. Paclitaxel, tanshinone II_A and tetrahydropalmatine were used to validate the law. Nanoparticles loaded silybin, puerarin, and ferulic acid with high drug loading efficiency were characterized by scan electron microscopy and DSC. Results The average size of mesoporous silica nanoparticles was (220 ± 21) nm, with a specific surface area of 353.53 m²/g, pore size of 1.53 nm and pore volume of about 0.4 cm³/g. In the condition of a fixed mass ratio of drug to mesoporous silica nanoparticles, the drug loading efficiency was always linearly related to the drug concentration at the above preparation technology even if drug loading of different drugs were analyzed together. No obvious drug crystallines were observed in the surface of nanoparticles by scan electron microscopy. Melting peaks of silybin, puerarin and ferulic acid were all observed in DSC curves of mesoporous silica nanoparticles loaded drugs, but their heat absorption amounts per mg were all smaller than physical mixtures. Conclusion The drug solution concentration was the key factor on drug loading efficiency of mesoporous silica nanoparticles by dipping centrifugation method and drugs existed in pores of mesoporous silica nanoparticles in crystalline and amorphous forms.

西南大学国家级大学生创新创业训练计划项目（201610635023）