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

使用聚（2-恶唑啉）/聚（2-恶嗪）两亲物的超高负载 API 纳米制剂的结构-性能关系

• 批准号: 398461692
• 负责人: Professor Dr. Robert Luxenhofer
• 金额: --
• 依托单位: Kemian osasto
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/398461692?language=en
• 关键词: Structure; property; relationships; ultra; loaded

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.

聚合物是一类非常重要的药用辅料。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）。聚合物胶束对于增加水不溶性药物的水溶性特别有用，并且已经为此目的进行了深入的研究。聚合物胶束的一个常见限制是其有限的药物负载和制剂稳定性。申请人已经研究了一段时间基于聚（2-恶唑啉）的特定聚合物平台，最近还研究了聚（2-恶嗪）。使用这些聚合物，可以获得具有异常高的药物负载（约100 μ g/ml）的稳定的药物负载胶束。50重量%分散相的浓度）和溶解度（药物浓度从约0.001 g/L至约50 g/L）。该项目的目的是阐明聚合物和药物结构之间的结构-性能关系，一方面和另一方面的药物负载。 为此，我们将相关的药物负载与从红外，拉曼和NMR光谱获得的分子药物/聚合物相互作用的数据。此外，我们还将载药量与聚合物和药物的溶解度参数以及胶束核的极性相关联。总之，我们期望详细了解分子结构-性质关系，这可以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设计有前途的药物-聚合物组合。