Adaption of nanocarrier-based drug delivery systems to the redox-state and thiol gradients of healthy and diseased skin

子项1将在高分子化学、皮肤学、物理化学等交叉学科的基础上，合成适用于抗炎药物转运的新型高分子纳米载体。它们被认为对发炎皮肤中的氧化还原过程和硫醇梯度反应敏感，因此它们的运输和释放活性物质可以通过使用雷帕霉素来控制。子项目2致力于皮肤病学研究，其中纳米载体应用于细胞和人体皮肤。细胞因子、氧化应激和酶活性在纳米载体的皮肤渗透和药物释放中的作用将被研究。此外，将在组织免疫细胞共培养中研究药物疗效，并确定雷帕霉素在炎症环境中由纳米载体运输的生物学效应。子项目3致力于高空间分辨率和无标签光谱显微镜。这尤其包括基于红外技术的x射线显微镜和原子力显微镜。这些方法用于定量确定活性物质的位置以及纳米载体及其分解产物作为生物条件和暴露时间的函数。所有子项目的紧密相互作用最终将提供一种新型纳米载体的基本概念，用于在皮肤病学局部应用的难以配制的药物的炎症部位进行有效的运输和选择性的控制释放。

In an interdisciplinary project, which includes polymer chemistry, dermatology, and physical chemistry, novel polymeric nanocarriers will be synthesized in subproject 1, which are suitable for the transport of anti-inflammatory drugs. These are supposed to react sensitively to redox processes and thiol gradients in the inflamed skin, so that their transport and release of the active substances can be controlled by using rapamycin as an example. Subproject 2 is dedicated to dermatological studies in which the nanocarriers are applied to both cells and human skin. The role of cytokines, oxidative stress, and enzymatic activity on skin penetration and drug release the use of nanocarriers will be investigated. Furthermore, drug efficacy will be investigated in tissue-immune cell co-cultures, and the biological effects of rapamycin transported by nanocarriers in inflamed environment will be determined. Subproject 3 is dedicated to high spatial resolution and label-free spectromicroscopy. This includes in particular X-ray microscopy and atomic force microscopy based infrared techniques. These methods are used to quantitatively determine the location of the active substances as well as the nanocarriers and their decomposition products as a function of biological conditions and exposure time. This tight interaction of all subprojects will finally deliver the basic concepts of a novel class of nanocarriers for the efficient transport and controlled release selectively at the site of inflammation of hard-to-formulate drugs for topical application in dermatology.