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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IIA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 prepare mesoporous silica nanoparticles (MSNs) containing different kinds of insoluble drugs by immersion centrifugation and explore the relationship between drug concentration and drug loading and the mechanism of drug loading of MSNs. Methods Blank MSNs were prepared and characterized by transmission electron microscopy (TEM) and nitrogen adsorption-desorption analysis. Taking silybin, puerarin, berberine hydrochloride, curcumin and ferulic acid as model drugs, respectively, the volume of drug solution and the drug quality were fixed. The drug loading was determined by immersion centrifugation. The drug loading was measured, Taxol, tanshinone IIA and tetrahydropalmatine were used to verify their drug loading. The silybin, puerarin and ferulic acid MSNs were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The drug-loading mechanism was analyzed. Results The size of blank MSNs was (220 ± 21) nm, the specific surface area was 353.53 m2 / g, the average pore size was 1.53 nm and the pore volume was about 0.4 cm3 / g. When the ratio of drug to drug remains the same, whether the volume of drug solution is fixed or the mass of drug fixed, the drug load is linear with the drug concentration, and has nothing to do with the nature of the drug, the comprehensive regression equations of the five drugs are fixed The drug solution volume Y = 0.351 7 X + 0.982 5, r = 0.991 4 and the fixed drug quality Y = 0.359 2 X + 0.248 3, r = 0.991 0. SEM showed no obvious drug crystals on the surface of drug-loaded MSNs. DSC of drug-loaded MSNs observed the melting peak of the drug, but the unit heat absorption was significantly lower than the proportion of the mechanical mixture. Conclusion The concentration of drug solution is the key factor to determine the drug-loading effect of MSNs impregnation centrifugation. The drug is mainly dispersed in the mesopores of MSNs in the form of amorphous and microcrystalline.