@article{FrombachUnbehauenKurniasihetal.2019,
  author    = {Frombach, Janna and Unbehauen, Michael and Kurniasih, Indah N. and Schumacher, Fabian and Volz, Pierre and Hadam, Sabrina and Rancan, Fiorenza and Blume-Peytavi, Ulrike and Kleuser, Burkhard and Haag, Rainer and Alexiev, Ulrike and Vogt, Annika},
  title     = {Core-multishell nanocarriers enhance drug penetration and reach keratinocytes and antigen-presenting cells in intact human skin},
  series = {Journal of controlled release},
  volume    = {299},
  journal   = {Journal of controlled release},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0168-3659},
  doi       = {10.1016/j.jconrel.2019.02.028},
  pages     = {138 -- 148},
  year      = {2019},
  abstract  = {In reconstructed skin and diffusion cell studies, core-multishell nanocarriers (CMS-NC) showed great potential for drug delivery across the skin barrier. Herein, we investigated penetration, release of dexamethasone (DXM), in excised full-thickness human skin with special focus on hair follicles (HF). Four hours and 16 h after topical application of clinically relevant dosages of 10 mu g DXM/cm(2) skin encapsulated in CMS-NC (12 nm diameter, 5.8\% loading), presence of DXM in the tissue as assessed by fluorescence microscopy of anti-DXM-stained tissue sections as well as ELISA and HPLC-MS/MS in tissue extracts was enhanced compared to standard LAW-creme but lower compared to DXM aqueous/alcoholic solution. Such enhanced penetration compared to conventional cremes offers high potential for topical therapies, as recurrent applications of corticosteroid solutions face limitations with regard to tolerability and fast drainage. The findings encourage more detailed investigations on where and how the nanocarrier and drug dissociate within the skin and what other factors, e.g. thermodynamic activity, influence the penetration of this formulations. Microscopic studies on the spatial distribution within the skin revealed accumulation in HF and furrows accompanied by limited cellular uptake assessed by flow cytometry (up to 9\% of total epidermal cells). FLIM clearly visualized the presence of CMS-NC in the viable epidermis and dermis. When exposed in situ a fraction of up to 25\% CD1a(+) cells were found within the epidermal CMS-NC+ population compared to approximately 3\% CD1a(+)/CMS-NC+ cells after in vitro exposure in short-term cultures of epidermal cell suspensions. The latter reflects the natural percentage of Langerhans cells (LC) in epidermis suspensions and indicated that CMS-NC were not preferentially internalized by one cell type. The increased CMS-NC+ LC proportion after exposure within the tissue is in accordance with the strategic suprabasal LC-localization. More specifically we postulate that the extensive dendrite meshwork, their position around HF orifices and their capacity to modulate tight junctions facilitated a preferential uptake of CMS-NC by LC within the skin. This newly identified aspect of CMS-NC penetration underlines the potential of CMS-NC for dermatotherapy and encourages further investigations of CMS-NC for the delivery of other molecule classes for which intracellular delivery is even more crucial.},
  language  = {en}
}
@article{LiSchlaichKulkaetal.2019,
  author    = {Li, Mingjun and Schlaich, Christoph and Kulka, Michael Willem and Donskyi, Ievgen S. and Schwerdtle, Tanja and Unger, Wolfgang E. S. and Haag, Rainer},
  title     = {Mussel-inspired coatings with tunable wettability, for enhanced antibacterial efficiency and reduced bacterial adhesion},
  series = {Journal of materials chemistry : B, Materials for biology and medicine},
  volume    = {7},
  journal   = {Journal of materials chemistry : B, Materials for biology and medicine},
  number    = {21},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2050-750X},
  doi       = {10.1039/c9tb00534j},
  pages     = {3438 -- 3445},
  year      = {2019},
  abstract  = {Over the last few decades, there has been a tremendous increase in research on antibacterial surface coatings as an alternative strategy against bacterial infections. Although there are several examples of effective strategies to prevent bacterial adhesion, the effect of the wetting properties on the coating was rarely considered as a crucial factor. Here we report an in-depth study on the effect of extreme wettability on the antibacterial efficiency of a silver nanoparticles ( AgNPs)-based coating. By controlling surface polymerization of mussel-inspired dendritic polyglycerol ( MI-dPG) and post-functionalization, surfaces with wetting properties ranging from superhydrophilic to superhydrophobic were fabricated. Subsequently, AgNPs were embedded into the coatings by applying in situ reduction using the free catechols-moieties present in the MI-dPG coating. The resulting polymer coatings exhibited excellent antibacterial ability against planktonic Escherichia coli ( E. coli) DH5a and Staphylococcus aureus ( S. aureus) SH1000. The antibacterial efficiency of the coatings was analyzed by using inductively coupled plasma mass spectrometry ( ICP-MS) and bacterial viability tests. Furthermore, the antifouling properties of the coatings in relation to the antibacterial properties were evaluated.},
  language  = {en}
}