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用赋形剂。它们可用于活性药物成分的控释或增加其表观溶解度（过饱和）。聚合物胶束在提高水不溶性药物的水溶性方面特别有用，并为此目的进行了深入的研究。聚合物胶束的一个常见的局限性是它们有限的药物负载和配方稳定性。申请人已经研究了一段时间的基于聚（2-恶唑啉）s的特定聚合物平台，最近也研究了聚（2-恶唑啉）s。使用这些聚合物，可以获得稳定的载药胶束，具有异常高的载药量(大约。50 wt.%的分散相)和溶解度(药物浓度从大约。约0.001 g/L。50 g / L)。本课题的目的是一方面阐明聚合物与药物结构之间的结构-性能关系，另一方面阐明药物负载关系。为此，我们将把药物装载与分子药物/聚合物相互作用的数据联系起来，这些数据来自红外、拉曼和核磁共振光谱。此外，我们将把载药量与聚合物和药物的溶解度参数以及胶束核的极性联系起来。总之，我们期望详细了解分子结构-性能关系，这可能解释为什么这种聚合物平台允许如此高的负载。反过来，这将使我们能够合理地设计有前途的药物-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.