Many natural compounds with interesting biomedical properties share one physicochemical property, namely, low water solubility. Polymer micelles are, among others, a popular means to solubilize hydrophobic compounds. The specific molecular interactions between the polymers and the hydrophobic drugs are diverse, and recently it has been discussed that macromolecular engineering can be used to optimize drug-loaded micelles. Specifically, π–π stacking between small molecules and polymers has been discussed as an important interaction that can be employed to increase drug loading and formulation stability. Here, we test this hypothesis using four different polymer amphiphiles with varying aromatic content and various natural products that also contain different relative amounts of aromatic moieties. In the case of paclitaxel, having the lowest relative content of aromatic moieties, the drug loading decreases with increasing relative aromatic amount in the polymer, whereas the drug loading of curcumin, having a much higher relative aromatic content, is increased. Interestingly, the loading using schizandrin A, a dibenzo[a,c]cyclooctadiene lignan with intermediate relative aromatic content is not influenced significantly by the aromatic content of the polymers employed. The very high drug loading, long-term stability, ability to form stable highly loaded binary coformulations in different drug combinations, small-sized formulations, and amorphous structures in all cases corroborate earlier reports that poly(2-oxazoline)-based micelles exhibit an extraordinarily high drug loading and are promising candidates for further biomedical applications. The presented results underline that the interaction between the polymers and the incorporated small molecules may be more complex and are significantly influenced by both sides, the used carrier and drug, and must be investigated in each specific case.

中文翻译：

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研究芳基部分对基于聚（2-恶唑啉）的两亲物疏水天然产物和药物配方的影响

许多具有令人感兴趣的生物医学特性的天然化合物具有一种物理化学特性，即低水溶性。聚合物胶束尤其是增溶疏水化合物的常用方法。聚合物与疏水性药物之间的特定分子相互作用是多种多样的，最近已经讨论了可以利用大分子工程来优化载药胶束。特别是，小分子与聚合物之间的π-π堆积已被讨论为可用于增加药物载量和制剂稳定性的重要相互作用。在这里，我们使用四种具有不同芳族含量的聚合物两亲物和各种天然产物（也包含不同相对数量的芳族部分）来检验该假设。如果是紫杉醇，具有相对低的芳族部分含量的聚合物，其载药量随着聚合物中相对芳族含量的增加而降低，而具有更高的相对芳族含量的姜黄素的载药量则增加。有趣的是，使用五味子素A（一种二苯并[具有相对相对芳族含量的a，c ]环辛二烯木脂素不受所用聚合物的芳族含量的显着影响。在所有情况下，非常高的载药量，长期稳定性，在不同药物组合中形成稳定的高载量二元共制剂，小尺寸制剂和无定形结构的能力在所有情况下均证实了较早的报道，即基于聚（2-恶唑啉）的胶束表现出极高的载药量，有望用于进一步的生物医学应用。提出的结果强调，聚合物与掺入的小分子之间的相互作用可能更复杂，并且受所用载体和药物的两面的影响很大，因此必须在每种具体情况下进行研究。