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

在一个跨学科的项目，其中包括聚合物化学，皮肤病学和物理化学，新的聚合物纳米载体将在子项目1中合成，这是适合于抗炎药物的运输。这些被认为对发炎皮肤中的氧化还原过程和硫醇梯度敏感地反应，使得它们的转运和活性物质的释放可以通过使用雷帕霉素作为示例来控制。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类皮肤。将研究细胞因子、氧化应激和酶活性对使用纳米载体的皮肤渗透和药物释放的作用。此外，将在组织-免疫细胞共培养物中研究药物功效，并将确定纳米载体在发炎环境中转运的雷帕霉素的生物学效应。子项目3致力于高空间分辨率和无标记光谱显微镜。这特别包括基于红外技术的X射线显微镜和原子力显微镜。这些方法用于定量测定活性物质以及纳米载体及其分解产物的位置，作为生物条件和暴露时间的函数。所有子项目的这种紧密相互作用最终将提供一类新型纳米载体的基本概念，用于在皮肤科局部应用的难以配制的药物的炎症部位选择性地进行有效运输和控制释放。

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.