Functional Polymer Materials, Chair for Chemical Technology of Material Synthesis and Bavarian Polymer Institute, Faculty of Chemistry and Pharmacy, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
ACS Appl Mater Interfaces. 2020 Jun 3;12(22):24531-24543. doi: 10.1021/acsami.9b22495. Epub 2020 May 26.
Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important, but previously largely ignored, factor for the rational design of polymeric micelles.
聚合物胶束通常被描述为核壳结构。疏水核被认为是疏水分子的储存库，而形成冠的嵌段则充当疏水核与水介质之间的稳定和增溶界面。人们已经付出了巨大的努力来调节疏水嵌段以增加胶束的载药量和稳定性，而在这种情况下，亲水嵌段的作用很少被研究，聚乙二醇（PEG）是亲水聚合物的金标准。为了更好地理解亲水冠的作用，研究了一系列基于聚（2-恶唑啉）和聚（2-恶嗪啉）的结构相似的 A-B-A 型两亲嵌段，通过改变亲水嵌段 A 利用聚（2-甲基-2-恶唑啉）（pMeOx；A）或聚（2-乙基-2-恶唑啉）（pEtOx；A*）。就亲水性而言，这两种聚合物都与 PEG 非常相似。更疏水的嵌段 B 带有聚（2-恶唑啉）和聚（2-恶嗪啉）主链，带有 C3（丙基）和 C4（丁基）侧链。令人惊讶的是，对于含有两种难溶于水的化合物姜黄素和紫杉醇的制剂，A-B-A > A*-B-A > A*-B-A* 的载药量差异很大，这突出了用于药物制剂的聚合物胶束亲水冠的重要性。还使用各种核磁共振波谱法、动态光散射、低温透射电子显微镜和（微）差示扫描量热法对制剂进行了表征。我们的研究结果表明，亲水嵌段与客体分子之间的相互作用应该被认为是聚合物胶束合理设计的一个重要但以前被广泛忽视的因素。
