Unravelling the mechanisms of drugs partitioning phenomena in micellar systems via NMR spectroscopy
Unravelling the mechanisms of drugs partitioning phenomena in micellar systems via NMR spectroscopy
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DOI：
10.1016/j.jcis.2023.01.063
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发表时间：
2023-02-01
影响因子：
9.9
通讯作者：
Nartowski, Karol P.
中科院分区：
文献类型：
--
作者：
Malec, Katarzyna;Monaco, Serena;Nartowski, Karol P.
尽管胶束在材料和胶体科学中广泛使用，但它们的超分子组织以及这些动态组装中的主客体相互作用却知之甚少。在胶束存在下的小客体分子经历胶束聚集体和周围溶液之间的恒定交换，对其分子水平表征构成相当大的挑战。在这项工作中，我们揭示了小客体分子和表面活性剂形成胶束通过新的应用程序的NMR技术支持与国家的最先进的分析方法在胶体科学之间的相互作用的地图。选择由结构上不同的表面活性剂（嵌段非离子聚合物Pluronic（R）F-127、非离子表面活性剂Tween 20或Tween 80和离子表面活性剂十二烷基硫酸钠SLS）组成的模型胶束，并加载已知具有不同分配系数的生物相关性的模型小分子（即药物氟康唑FLU或吲哚美辛IMC）。结合NMR方法（1D 1H NMR、1D 19 F NMR、2D 1H-1H NOESY和2D 1H-19 F HOESY以及多频-STD NMR）建立了胶束聚集体的亲水和疏水区域内的FLU或IMC的分子水平组织，并与分子动力学（MD）模拟相证实。这是第一次应用多频STD NMR胶体系统，使我们能够阐明错综复杂的详细模式的药物/胶束相互作用在一个单一的NMR实验在几分钟内。重要的是，我们的研究结果表明，灵活的表面活性剂，如嵌段共聚物和聚山梨醇酯，形成胶束聚集体的表面组成的亲水性和疏水性域，并不遵循经典的核-壳模型的胶束。我们建议，1H化学位移的变化幅度与从DEEP-STD NMR和2D NMR实验获得的相互作用图证实，可以用作客人-表面活性剂相互作用的强度的指标。该NMR工具箱可用于从软材料到生物系统的广泛胶体主客体系统的分析。(c)2023爱思唯尔公司All rights reserved.
Despite extensive use of micelles in materials and colloidal science, their supramolecular organization as well as host-guest interactions within these dynamic assemblies are poorly understood. Small guest molecules in the presence of micelles undergo constant exchange between a micellar aggregate and the surrounding solution, posing a considerable challenge for their molecular level characterisation. In this work we reveal the interaction maps between small guest molecules and surfactants forming micelles via novel applications of NMR techniques supported with state-of-the-art analytical methods used in colloidal science. Model micelles composed of structurally distinct surfactants (block non-ionic polymer Pluronic (R) F-127, non-ionic surfactant Tween 20 or Tween 80, and ionic surfactant sodium lauryl sulphate, SLS) were selected and loaded with model small molecules of biological relevance (i.e. the drugs fluconazole, FLU or indomethacin, IMC) known to have different partition coefficients. Molecular level organization of FLU or IMC within hydrophilic and hydrophobic domains of micellar aggregates was established using the combination of NMR methods (1D 1H NMR, 1D 19F NMR, 2D 1H-1H NOESY and 2D 1H-19F HOESY, and the multifrequency-STD NMR) and corroborated with molecular dynamics (MD) simulations. This is the first application of multifrequency-STD NMR to colloidal systems, enabling us to elucidate intricately detailed patterns of drug/micelle interactions in a single NMR experiment within minutes. Importantly, our results indicate that flexible surfactants, such as block copolymers and polysorbates, form micellar aggregates with a surface composed of both hydrophilic and hydrophobic domains and do not follow the classical core-shell model of the micelle. We propose that the magnitude of changes in 1H chemical shifts corroborated with interaction maps obtained from DEEP-STD NMR and 2D NMR experiments can be used as an indicator of the strength of the guest-surfactant interactions. This NMR toolbox can be adopted for the analysis of broad range of colloidal host-guest systems from soft materials to biological systems.(c) 2023 Elsevier Inc. All rights reserved.