响应面法优化中空介孔二氧化硅球包载吲哚美辛的工艺研究

Optimization of indomethacin loaded hollow mesoporous silica nanoparticles by response surface method

采用硬模板法在室温下、中性水溶液中合成了中空介孔二氧化硅球,中空部分直径为250nm,外壳厚度25nm。利用氮气吸附-解吸附、透射电子显微镜、傅里叶变换红外光谱表征了微球的物理化学性质。该微球球形度良好,BET结果显示其比表面积为730.0m^2/g,平均孔容1.084cm^3/g,平均孔道直径6.58nm。利用中空介孔二氧化硅球较好的载药性能负载吲哚美辛,并采用三因素的Box-Behnke实验设计对药物负载处方工艺进行优化研究。当IMC/HMSNs质量比为22:1,超声1.4h,震荡吸附23h时实验条件达到最佳,包封率理论值为85.2%。在此条件进行验证实验,吲哚美辛的包封率可达理论预测值的98.7%,说明将Box-Behnken实验设计法用于中空介孔二氧化硅球包载吲哚美辛的优化筛选是可行的,且得到的实验观察值与数学模型的预测值相符合。

The hollow mesoporous silica nanoparticles（HMSN） were synthesized in neutral aqueous solution at room temperature. Following this method,well-defined HMSN was prepared with a 25 nm shell and a 250 nm hollow diameter. Nitrogen adsorption-desorption analysis,Trans-mission electron microscopy,Fourier Transform Infrared Spectrometer were applied to characterize the synthesized HMSNs. The morphology of the HMSN was spherical. The BET result shows that the specific surface area of HMSN was 730.0m^2/g,the average pore size was 1.084cm^3/g,and the pore diameter was 6.58 nm. Experiments were designed according to a three-level Box-Behnken design to optimize the Indomethacin loaded HMSNs. The result indicated that HMSNs exhibited an excellent drug loading capacity. The optimal formulation parameters were as follows：IMC/HMSNs mass ratios（A）,loading time（B） and ultrasonic time（C） levels were 22 ∶ 1, 1.4h and 23 h, respectively and the best encapsulation efficiency could be 85.2%. The observed responses were in good agreement with the predicted values of the mathematic models,so the Box-Behnken design is suitable for optimizing the formulation of indomethacin loaded hollow mesoporous silica nanoparticles.