Structure-property relationships in ultra-high loaded API nanoformulation using poly(2-oxazoline)/poly(2-oxazine) amphiphiles

聚合物是一类非常重要的药物辅料。它们可用于有效药物成分的控制释放或增加其表观溶解度(过饱和)。聚合物胶束特别有助于增加水不溶性药物的水溶解度，并为此进行了深入的研究。聚合物胶束通常注意到的局限性之一是其载药量和配方稳定性有限。申请人已经研究了一段时间基于聚(2-恶唑啉)S和最近还基于聚(2-恶唑啉)S的特定聚合物平台。使用这些聚合物，有可能获得稳定的载药量胶束，具有异常高的载药量(约)。分散相的50wt.%)和溶解度(药物浓度从约0.001克/L，约50g/L)。本项目的目的一方面是阐明聚合物和药物结构之间的结构-性质关系，另一方面是阐明药物的载药量。为此，我们将药物负载量与红外、拉曼和核磁共振光谱获得的分子药物/聚合物相互作用数据进行关联。此外，我们还将药物载量与聚合物和药物的溶解度参数以及胶束核的极性进行关联。总之，我们期待对分子结构-性质关系的详细了解，这可能解释为什么这个聚合物平台允许如此高的负载量。反过来，这将使我们能够合理设计有前景的药物-聚合物组合。

Polymers are a very important class of pharmaceutical excipients. They can be utilized for controlled release of active pharmaceutical ingredients or to increase their apparent solubility (supersaturation). Polymer micelles are particularly useful to increase the aqueous solubility of water-insoluble drugs and have been investigated to this end intensively. One of the commonly noted limitations of polymer micelles is their limited drug loading and formulation stability. The applicant has investigated for some time a particular polymer platform on the basis of poly(2-oxazoline)s and recently also poly(2-oxazine)s. With these polymers, it was possible to obtain stably drug loaded micelles with an unusually high drug loading (approx. 50 wt.% of dispersed phase) and solubility (increase of drug concentration from approx. 0.001 g/L to approx. 50 g/L). The aim of this project is the elucidation of structure-property relationships between polymer and drug structure on the one hand and the drug loading on the other hand. To this end, we will correlate the drug loading with data on the molecular drug/polymer interactions obtained from infrared, Raman and NMR-spectroscopy. In addition, we will correlate the drug loading with the solubility parameter of the polymers and drugs as well as the polarity of the micellar core. In summary, we expect a detailed understanding of the molecular structure-property relationships which may explain why this polymer platform allows such extraordinary high loading. This, in turn, will allow us the rational design of promising drug-polymer combinations.