Block copolymer micelles have been increasingly used for the solubilization and delivery of hydrophobic drugs. There exists a possibility of dissociation of micelles and formation of other association structures in contact with the gastrointestinal fluid. In this study, we demonstrated the effect of the fed-state intestinal fluid (FeSSIF) upon characteristics of bare and quercetin (QCT)-loaded pluronic 123 (P123) micelles. Characterizations were performed using dynamic light scattering (DLS), ¹H NMR, heteronuclear single-quantum coherence (HSQC), two-dimensional ¹H–¹H nuclear Overhauser effect spectroscopy (2D-NOESY), and diffusion-ordered spectroscopy (DOSY). In the case of bare micelles, we found copolymer–bile salt mixed aggregates without any noticeable change in size. DOSY data revealed that lecithin formed a separate aggregate in the FeSSIF. Complete micellar solubilization of QCT could be verified by the disappearance of its proton signals. At higher dose levels, the diffusion coefficient of micelles increased in the FeSSIF. We speculate that QCT-induced hydrophobicity and availability of FeSSIF components would have driven the formation of small-sized mixed assemblies. On the contrary, the diffusion coefficient of micelles decreased with an increase in the QCT load in the medium devoid of FeSSIF components. We deduce that lack of lecithin and bile salts precluded the formation of mixed assemblies in this case, and therefore, micelles turned heavier at higher QCT loads. Such insights on self-assembled formulations can be valuable in improving their biological performance.

中文翻译：

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人工胃肠道培养基中裸露和槲皮素负载的非离子嵌段共聚物胶束的比较分析


嵌段共聚物胶束已越来越多地用于疏水药物的增溶和递送。与胃肠道液接触时，存在胶束解离和形成其他关联结构的可能性。在这项研究中，我们证明了饲养状态肠液 （FeSSIF） 对裸露和槲皮素 （QCT） 负载的普朗尼克 123 （P123） 胶束特性的影响。使用动态光散射 （DLS）、¹H NMR、异核单量子相干 （HSQC）、二维 ¹H–¹H 核 Overhauser 效应光谱 （2D-NOESY） 和扩散有序光谱 （DOSY） 进行表征。在裸露胶束的情况下，我们发现共聚物-胆盐混合聚集体的大小没有任何明显的变化。DOSY 数据显示卵磷脂在 FeSSIF 中形成单独的聚集体。QCT 的完全胶束溶解可以通过其质子信号的消失来验证。在较高剂量水平下，FeSSIF 中胶束的扩散系数增加。我们推测 QCT 诱导的疏水性和 FeSSIF 组件的可用性会驱动小尺寸混合组件的形成。相反，在不含 FeSSIF 组分的培养基中，胶束的扩散系数随着 QCT 负载量的增加而降低。我们推断，在这种情况下，缺乏卵磷脂和胆汁盐排除了混合组装体的形成，因此，胶束在较高的 QCT 负载下变得更重。这种对自组装配方的见解对于提高其生物性能很有价值。