目的 研究介孔二氧化硅納米粒（MSN）載體與裝載的難溶性藥物間的相互作用，探索對釋放速率具有重要影響的因素，歸納總結(jié)可預測難溶性藥物-MSN給藥系統(tǒng)釋放行為的數(shù)學模型。方法 以溶膠凝膠法制備的MSN作為載體，通過溶劑揮干法進行藥物裝載，利用掃描電子顯微鏡（SEM）、透射電子顯微鏡（TEM）分析載體的外觀形貌及孔道結(jié)構(gòu)，通過比表面積分析儀研究載體的比表面積及孔徑分布。選取載藥量及藥物的氫鍵受體數(shù)量作為因素進行釋放行為分析，通過Design Expert軟件進行2因素3水平析因設計，完成體外釋放實驗；2、24 h累積釋放度作為因變量，擬合數(shù)學模型。結(jié)果溶膠凝膠法制備的MSN為均一的球形，粒徑約為400 nm，孔道呈放射狀，孔徑均一為3.6 nm。擬合模型顯示，載藥量比氫鍵受體數(shù)量對2 h累計釋放度影響更大，隨著載藥量的增加，2 h累計釋放度逐漸下降；在研究范圍內(nèi)，氫鍵受體數(shù)為6，載藥量為50%具有最小的2 h累計釋放度，為50.31%。24 h累計釋放度則根據(jù)載藥量的不同隨著氫鍵受體數(shù)的改變呈現(xiàn)相反趨勢，當載藥量較低時，與氫鍵受體數(shù)呈正相關；當載藥量較高時，與氫鍵受體數(shù)呈負相關。氫鍵受體數(shù)為6，載藥量小于10%時具有最大的24 h累計釋放度，可達99.44%。結(jié)論 相對藥物的氫鍵受體數(shù)量，載藥量對于難溶性藥物-MSN給藥系統(tǒng)的速緩釋放具有重要調(diào)控作用，低載藥量可以實現(xiàn)藥物的2 h快速釋放及24 h完全釋放，高載藥量則反之。

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.

國家自然科學基金青年基金項目（81703427）；遼寧省科學技術計劃項目（2014226033）；中國醫(yī)科大學校內(nèi)課題基金（XZR20160007）；中國醫(yī)科大學附屬第一醫(yī)院院內(nèi)基金（FSFH201717）。