Nanostructures and Dynamics of Isochorically Confined Amorphous Drug Mediated by Cooling Rate, Interfacial, and Intermolecular Interactions
Nanostructures and Dynamics of Isochorically Confined Amorphous Drug Mediated by Cooling Rate, Interfacial, and Intermolecular Interactions
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冷却速率、界面和分子间相互作用介导的等容限域非晶态药物的纳米结构和动力学
DOI：
10.1021/acs.jpcb.7b08545
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发表时间：
2017
影响因子：
3.3
通讯作者：
Xue Gi
中科院分区：
文献类型：
--
作者：
Zhang Chen;Sha Ye;Zhang Yue;Cai Ting;Li Linling;Zhou Dongshan;Wang Xiaoliang;Xue Gi
利用纳米约束效应制备和稳定无定形药物是近年来药学领域的研究热点。本文采用差示扫描量热法（DSC）和宽带介电谱（BDS）研究了吲哚美辛（IMC）和灰黄霉素（GSF）在不同孔径（25-250 nm）的阳极氧化铝（AAO）模板中的主客体体系。受限药物的结晶受到抑制，并且它们的玻璃化转变温度显示出明显的孔径依赖性。此外，介电和量热结果的组合表明，在冷却过程中的结构弛豫时间的温度依赖性的显着变化是由于玻璃化的界面分子和局部密度不均匀性下等容限制。有趣的是，与IMC/AAO的典型两层模型相比，GSF/AAO在快速冷却（40-10 K/min）下出现了罕见的三个玻璃化转变温度，表明在体块状芯层和界面层之间存在热力学非平衡夹层。相比之下，缓慢冷却过程（0.5 K/min）将导致受限的GSF进入稳定的核-壳纳米结构。通过表面改性，证实了界面效应是导致这两种客体/主体体系之间存在不同现象的重要原因，同时考虑到界面相互作用的长程效应，建议重视分子间氢键作用。我们的结果不仅提供了洞察几何限制过冷液体的玻璃化转变行为，但也提供了一种手段，调整和稳定的纳米结构的非晶药物在二维限制。
The production and stabilization of amorphous drugs by the nanoconfinement effect has recently become a research hotspot in pharmaceutical sciences. Herein, two guest/host systems, indomethacin (IMC) and griseofulvin (GSF) confined in anodic aluminum oxide (AAO) templates with different pore diameters (25–250 nm) are investigated by differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). The crystallization of the confined drugs is suppressed, and their glass transition temperatures show an evident pore-size dependency. Moreover, a combination of dielectric and calorimetric results demonstrates that the significant change in the temperature dependence of the structural relaxation time during the cooling process is attributed to the vitrification of the interfacial molecules and the local density heterogeneity under isochoric confinement. Interestingly, compared with the case of IMC/AAO, which can be described by a typical two-layer model, GSF/AAO presents an rare scenario of three glass transition temperatures under fast cooling (40–10 K/min), indicating that there exists a thermodynamic nonequilibrium interlayer between the bulk-like core and interfacial layer. In contrast, the slow cooling process (0.5 K/min) would lead confined GSF into the stable core–shell nanostructure. Using surface modification, the interfacial effect is confirmed to be an important reason for the different phenomena between these two guest/host systems, and intermolecular hydrogen bonding is also suggested to be emphasized considering the long-range effect of interfacial interactions. Our results not only provide insight into the glass transition behavior of geometrically confined supercooled liquids, but also offer a means of adjusting and stabilizing the nanostructure of amorphous drugs under two-dimensional confinement.