@article{WanjikuYamamotoKlosseketal.2019, author = {Wanjiku, Barbara and Yamamoto, Kenji and Klossek, Andre and Schumacher, Fabian and Pischon, Hannah and Mundhenk, Lars and Rancan, Fiorenza and Judd, Martyna M. and Ahmed, Muniruddin and Zoschke, Christian and Kleuser, Burkhard and R{\"u}hl, Eckart and Sch{\"a}fer-Korting, Monika}, title = {Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration}, series = {Analytical chemistry}, volume = {91}, journal = {Analytical chemistry}, number = {11}, publisher = {American Chemical Society}, address = {Washington}, issn = {0003-2700}, doi = {10.1021/acs.analchem.9b00519}, pages = {7208 -- 7214}, year = {2019}, abstract = {Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.}, language = {en} } @inproceedings{FrombachRancanFleigeetal.2015, author = {Frombach, Janna and Rancan, Fiorenza and Fleige, Emanuel and Haag, Rainer and Schumacher, Frank and Kleuser, Burkhard and Yamamoto, Kenji and R{\"u}hl, Eckart and Blume-Peytavi, Ulrike and Vogt, Annika}, title = {Skin penetration and dexamethasone release from polymer nanoparticles in ex vivo human skin}, series = {The journal of investigative dermatology}, volume = {135}, booktitle = {The journal of investigative dermatology}, publisher = {Nature Publ. Group}, address = {New York}, issn = {0022-202X}, pages = {S52 -- S52}, year = {2015}, language = {en} } @article{RancanWieheNoebeletal.2005, author = {Rancan, Fiorenza and Wiehe, Arno and N{\"o}bel, Maria and Senge, Mathias O and Al Omari, Saleh and B{\"o}hm, Fritz and John, Matthias and R{\"o}der, Beate}, title = {Influence of substitutions on asymmetric dihydroxychlorins with regard to intracellular uptake, subcellular localization and photosensitization of Jurkat cells}, issn = {1011-1344}, year = {2005}, abstract = {The search for new efficient sensitizers for photodynamic therapy (PDT) points to improve photophysical properties like absorption in the red region and singlet oxygen quantum yield as well as to control the localization of the sensitizer within the tumour cell. Depending on their physicochemical properties and their uptake mechanism, sensitizers can reach different intracellular concentrations and localize in different subcellular compartments. Moreover, the preferential localization of a sensitizer in target organelles, like mitochondria or lysosomes, could determine the cell death mechanism after PDT. This study aimed to investigate the influence of substitutions on dihydroxychlorins with regard to intracellular uptake, subcellular localization and cell death pathway. Moreover, the effect of a liposome-based delivery system was tested. The intracellular uptake was found to be strictly dependent on the sensitizer molecular structure and the means of its delivery. The most polar sensitizer in this study (compound 3) had, depending on incubation time, an intracellular concentration 2-8 times higher than the unsubstituted chlorin 1. All investigated photosensitizers localize predominantly in lysosomes but after longer incubation times weak fluorescence intensity was also detected in mitochondria and Golgi apparatus. The cell death pathway was found to be influenced by the sensitizer intracellular concentration and the applied light doses. In general, the increasing amphiphilicity of the sensitizer molecules is correlated with an increased sensitizer uptake and an increased rate of necrotic cells after irradiation. (C) 2004 Elsevier B.V. All rights reserved}, language = {en} }