Computational Models of the Intestinal Environment. 3. The Impact of Cholesterol Content and pH on Mixed Micelle Colloids.
Computational Models of the Intestinal Environment. 3. The Impact of Cholesterol Content and pH on Mixed Micelle Colloids.
复制标题
肠道环境的计算模型。
作者：
Estelle J A Suys;Dallas B. Warren;C. Porter;H. Benameur;C. Pouton;D. Chalmers
在这项研究中，我们使用分子动力学（MD）和实验技术（比浊法和动态光散射）的胆固醇含量和pH值的影响，形成在胃肠道（GI）道脂质消化后的胶体结构。我们证明，分子物质的电离状态是模型胆汁形成的聚集体自组装的主要驱动因素，因此在对胶体药物递送系统进行计算机模拟时应该考虑。此外，在模型系统内掺入生理浓度的胆固醇不会显著影响聚集体的大小、数量、形状或动力学。MD数据显示，随着pH值的增加，聚集体的大小减少，优先选择glycodeoxycholate（GDX）占据聚集体表面，并且混合胶束聚集体是扁球形（盘状）。所获得的结果有助于了解的过程中，pH值和胆固醇的影响自组装的混合胶束内的胃肠道。MD方法为研究药物和制剂辅料与胃肠道内源性内容物的相互作用提供了一个平台。
In this study, we use molecular dynamics (MD) and experimental techniques (nephelometry and dynamic light scattering) to investigate the influence of cholesterol content and pH on the colloidal structures that form in the gastrointestinal (GI) tract upon lipid digestion. We demonstrate that the ionization state of the molecular species is a primary driver for the self-assembly of aggregates formed by model bile and therefore should be considered when performing in silico modeling of colloidal drug delivery systems. Additionally, the incorporation of physiological concentrations of cholesterol within the model systems does not affect size, number, shape, or dynamics of the aggregates to a significant degree. The MD data shows a reduction in aggregate size with increasing pH, a preference for glycodeoxycholate (GDX) to occupy the aggregate surface, and that the mixed micellar aggregates are oblate spheroids (disc-like). The results obtained assist in understanding the process by which pH and cholesterol influence self-assembly of mixed micelles within the GI tract. The MD approach provides a platform for investigation of interactions of drugs and formulation excipients with the endogenous contents of the GI tract.
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影响因子：
9.9
作者：
Rezhdo O;Di Maio S;Le P;Littrell KC;Carrier RL;Chen SH
通讯作者：
Chen SH
影响因子：
2.9
作者：
HERNELL, O;STAGGERS, JE;CAREY, MC
通讯作者：
CAREY, MC
胆盐/卵磷脂混合胶束的结构二态性。
影响因子：
2.9
作者：
Müller,K
通讯作者：
Müller,K
影响因子：
2.9
作者：
CISTOLA, DP;HAMILTON, JA;SMALL, DM
通讯作者：
SMALL, DM