难溶性药物与介孔二氧化硅纳米粒载体的相互作用对于释放速率的影响

目的 研究介孔二氧化硅纳米粒（MSN）载体与装载的难溶性药物间的相互作用，探索对释放速率具有重要影响的因素，归纳总结可预测难溶性药物-MSN给药系统释放行为的数学模型。方法 以溶胶凝胶法制备的MSN作为载体，通过溶剂挥干法进行药物装载，利用扫描电子显微镜（SEM）、透射电子显微镜（TEM）分析载体的外观形貌及孔道结构，通过比表面积分析仪研究载体的比表面积及孔径分布。选取载药量及药物的氢键受体数量作为因素进行释放行为分析，通过Design Expert软件进行2因素3水平析因设计，完成体外释放实验；2、24 h累积释放度作为因变量，拟合数学模型。结果溶胶凝胶法制备的MSN为均一的球形，粒径约为400 nm，孔道呈放射状，孔径均一为3.6 nm。拟合模型显示，载药量比氢键受体数量对2 h累计释放度影响更大，随着载药量的增加，2 h累计释放度逐渐下降；在研究范围内，氢键受体数为6，载药量为50%具有最小的2 h累计释放度，为50.31%。24 h累计释放度则根据载药量的不同随着氢键受体数的改变呈现相反趋势，当载药量较低时，与氢键受体数呈正相关；当载药量较高时，与氢键受体数呈负相关。氢键受体数为6，载药量小于10%时具有最大的24 h累计释放度，可达99.44%。结论 相对药物的氢键受体数量，载药量对于难溶性药物-MSN给药系统的速缓释放具有重要调控作用，低载药量可以实现药物的2 h快速释放及24 h完全释放，高载药量则反之。

Influence of interaction between insoluble drug and mesoporous silica nanoparticle carriers on release rate

Objective To research the interaction between mesoporous silica nanoparticle (MSN) carriers and loaded poorly-water soluble drugs, and exploring the factors that have important impacts on release rate. A mathematical model for predicting the release behavior of insoluble drugs-mesoporous silica delivery system was summarized. Methods Sol-gel method was used to prepare mesoporous silica carriers. Solvent evaporation method was used to load drugs. The morphology and pore structure of the carrier were analyzed by SEM and TEM. The specific surface area and pore size distribution of the carrier were studied by the specific surface area analyzer. The drug loading amount and drug hydrogen bonding receptor were selected as the factors to analyze the release behavior. The release experiments of two factors-three levels were performed by Design Expert software, and the in vitro release experiments were carried out. The mathematical model was fitted with 2 h and 24 h accumulative release amount as dependent variables.Results The MSN prepared by sol-gel method was spherical, with a diameter of about 400 nm and a radial pore with an uniform pore size of 3.6 nm. The fitting model showed that, the 2 h accumulative release amount was more affected by drug loading than by the number of hydrogen bonding acceptors. With the increase of drug loading, the 2 h accumulative release amount decreased gradually. If the number of hydrogen bonding acceptors is 6 and the drug loading is 50%, 50.31% will be the minimum 2 h accumulative release amount within the range of this study. The 24 h accumulative release amount showed the opposite trend with the change of the number of hydrogen-bonded receptors according to the drug loading. When the drug loading was low, it was positively correlated with the number of hydrogen-bonded receptors; when the drug loading was high, it was negatively correlated with the number of hydrogen-bonded receptors.And if the number of hydrogen bonding acceptors is 6 and the drug loading is 10%, there will be the maximum 24 h accumulative release of 99.44%. Conclusions The effect of the number of hydrogen bonding receptors on the release behavior of drugs is not very significant. In contrast, drug loading has an important effect on drug release rate. Low drug loading can achieve the rapid release of 2 h, and the complete release of 24 h, and high drug loading had the adverse trends.