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

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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.