Department of Pharmaceutics, Shenyang Pharmaceutical University, Liaoning Province, People's Republic of China.
Int J Nanomedicine. 2013;8:4015-31. doi: 10.2147/IJN.S52605. Epub 2013 Oct 22.
The goal of the present study was to compare the drug release properties and stability of the nanoporous silica with different pore architectures as a matrix for improved delivery of poorly soluble drugs. For this purpose, three dimensional ordered macroporous (3DOM) silica with 3D continuous and interconnected macropores of different sizes (200 nm and 500 nm) and classic mesoporous silica (ie, Mobil Composition of Matter [MCM]-41 and Santa Barbara Amorphous [SBA]-15) with well-ordered two dimensional (2D) cylindrical mesopores were successfully fabricated and then loaded with the model drug indomethacin (IMC) via the solvent deposition method. Scanning electron microscopy (SEM), N2 adsorption, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were applied to systematically characterize all IMC-loaded nanoporous silica formulations, evidencing the successful inclusion of IMC into nanopores, the reduced crystallinity, and finally accelerated dissolution of IMC. It was worth mentioning that, in comparison to 2D mesoporous silica, 3DOM silica displayed a more rapid release profile, which may be ascribed to the 3D interconnected pore networks and the highly accessible surface areas. The results obtained from the stability test indicated that the amorphous state of IMC entrapped in the 2D mesoporous silica (SBA-15 and MCM-41) has a better physical stability than in that of 3DOM silica. Moreover, the dissolution rate and stability of IMC loaded in 3DOM silica was closely related to the pore size of macroporous silica. The colorimetric 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Cell Counting Kit (CCK)-8 assays in combination with direct morphology observations demonstrated the good biocompatibility of nanoporous silica, especially for 3DOM silica and SBA-15. The present work encourages further study of the drug release properties and stability of drug entrapped in different pore architecture of silica in order to realize their potential in oral drug delivery.
本研究的目的是比较具有不同孔结构的纳米孔硅作为改善难溶性药物传递的基质的药物释放特性和稳定性。为此，成功制备了具有不同尺寸（200nm 和 500nm）的三维有序大孔（3DOM）硅和具有有序二维（2D）圆柱形介孔的经典介孔硅（即 Mobil Composition of Matter [MCM]-41 和 Santa Barbara Amorphous [SBA]-15），然后通过溶剂沉积法将模型药物吲哚美辛（IMC）载入其中。扫描电子显微镜（SEM）、N2 吸附、差示扫描量热法（DSC）和 X 射线衍射（XRD）被应用于系统地表征所有 IMC 负载的纳米孔硅制剂，证明了 IMC 成功地进入了纳米孔，结晶度降低，最终 IMC 的溶解速度加快。值得一提的是，与 2D 介孔硅相比，3DOM 硅显示出更快的释放曲线，这可能归因于 3D 互连通孔网络和高可及表面积。稳定性测试的结果表明，在 2D 介孔硅（SBA-15 和 MCM-41）中包埋的 IMC 的无定形状态比在 3DOM 硅中具有更好的物理稳定性。此外，负载在 3DOM 硅中的 IMC 的溶解速率和稳定性与大孔硅的孔径密切相关。比色 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物（MTT）和细胞计数试剂盒（CCK）-8 测定法与直接形态观察相结合，证明了纳米孔硅的良好生物相容性，特别是 3DOM 硅和 SBA-15。本工作鼓励进一步研究不同孔结构的硅中包埋药物的药物释放特性和稳定性，以实现其在口服药物传递中的潜力。
