Solubilisation and Release of Organic Compounds of Different Polarity by Interpolyelectrolyte Complexes Based on Block Copolymer Micelles

基于嵌段共聚物胶束的互聚电解质复合物增溶和释放不同极性的有机化合物

• 批准号: 402765656
• 负责人: Professor Dr. Michael Gradzielski
• 金额: --
• 依托单位: Arbeitsgruppe Physikalische Chemie/ Molekulare Materialwissenschaften
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/402765656?language=en
• 关键词: Solubilisation; Release; Organic; Compounds; Different

The main aim of this project is to develop well-defined core-shell-corona IPEC micelles and to investigate them with respect to their solubilisation and release properties. For that purpose we start from amphiphilic block copolymers of the poly(alkylacrylate)-b-poly(acrylic acid) (PAlkA-b-PAA) type, which form micelles in aqueous solution and will be synthesised in this project. By addition of a polycation a shell of an interpolyelectrolyte complex (IPEC) is formed to produce copolymer IPEC micelles. As an interesting variation we will employ double-hydrophilic diblock copolymers with a neutral block as polycations. The properties of this shell are controlled by the choice of polycation, and the hydrophobicity of the micellar core via the length of the alkyl chain of the PAlkA. In addition, the size of core and shell will be controlled by the length of the PAlkA block and the amount of the added polycation, respectively. As a first step we will characterise in detail the structure of these IPEC micelles as a function of their molecular building blocks in order to determine systematic correlations between them. Here we will mainly employ scattering techniques and fluorescence measurements. In the second step we will determine the solubilisation capacity for oils of different polarity for differently sized and structured IPEC micelles. Structural changes of the IPEC micelles induced by solubilisation as well as the solubilisation site (core and/or shell) will be determined. From that systematic correlations between the polarities of the oil, micelle core and IPEC shell and the solubilisation site and the resulting structural changes will be deduced. Here we will also use drug molecules as polar solubilisates, which are expected to become solubilized preferentially in the IPEC shell. Having a multi-compartment systems we expect to be able to form aggregates with solubilisates of different polarity in the different regions of core and shell, thereby opening the path to delivery systems that are able to carry both, unpolar and polar active agents at the same time. As we are working with PAA stabilized systems we will then study the pH response of these loaded IPEC micelles in the relevant pH range of 5-8. The focus will be on structural changes occurring as well as on the release kinetics for different active agents (payload) contained. The release will in general depend on structure and molecular composition of the IPEC micelles, as well as on pH, which means it can be triggered by a pH-change. This will mainly be studied by fluorescence measurements (high sensitivity) and allows to determine how versatile the IPEC-micelles can be tuned for such release experiments. In general, the comprehensive characterisation of these complex colloids will yield a substantial advancement of the scientific understanding for using IPEC micelles for selective solubilisation and release, thereby bringing such systems closer to potential applications.

该项目的主要目的是开发定义明确的核-壳-冠IPEC胶束，并研究它们的增溶和释放特性。为此，我们从聚（丙烯酸烷基酯）-b-聚（丙烯酸）（PAkA-b-PAA）类型的两亲性嵌段共聚物开始，其在水溶液中形成胶束，并将在本项目中合成。通过添加聚阳离子，形成插层复合物（IPEC）的壳以产生共聚物IPEC胶束。作为一个有趣的变化，我们将采用具有中性嵌段的双亲水性二嵌段共聚物作为聚阳离子。该壳的性质由聚阳离子的选择和胶束核的疏水性通过PAkA的烷基链的长度来控制。此外，核和壳的尺寸将分别由PAkA嵌段的长度和添加的聚阳离子的量控制。作为第一步，我们将详细研究这些IPEC胶束的结构作为其分子构建块的函数，以确定它们之间的系统相关性。在这里，我们将主要采用散射技术和荧光测量。在第二步中，我们将确定不同大小和结构的IPEC胶束对不同极性油的增溶能力。将确定溶解诱导的IPEC胶束的结构变化以及溶解位点（核和/或壳）。从该系统之间的相关性的极性的油，胶束核心和IPEC壳和增溶位点和由此产生的结构变化将被推断。在这里，我们还将使用药物分子作为极性增溶剂，预期其优先溶解在IPEC壳中。具有多隔室系统，我们期望能够在核和壳的不同区域中与不同极性的增溶物形成聚集体，从而打开能够同时携带非极性和极性活性剂的递送系统的途径。当我们使用PAA稳定的体系时，我们将研究这些负载的IPEC胶束在5-8的相关pH范围内的pH响应。重点将放在结构变化的发生，以及对不同的活性剂（有效载荷）的释放动力学。释放通常取决于IPEC胶束的结构和分子组成以及pH，这意味着它可以通过pH变化触发。这将主要通过荧光测量（高灵敏度）进行研究，并允许确定IPEC胶束的通用性如何调整用于此类释放实验。一般来说，这些复杂胶体的全面表征将产生使用IPEC胶束进行选择性溶解和释放的科学理解的实质性进步，从而使这种系统更接近潜在的应用。