@article{HoenzkeGereckeElpeltetal.2016,
  author    = {H{\"o}nzke, Stefan and Gerecke, Christian and Elpelt, Anja and Zhang, Nan and Unbehauen, Michael and Kral, Vivian and Fleige, Emanuel and Paulus, Florian and Haag, Rainer and Sch{\"a}fer-Korting, Monika and Kleuser, Burkhard and Hedtrich, Sarah},
  title     = {Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing},
  series = {Journal of controlled release},
  volume    = {242},
  journal   = {Journal of controlled release},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0168-3659},
  doi       = {10.1016/j.jconrel.2016.06.030},
  pages     = {50 -- 63},
  year      = {2016},
  abstract  = {Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester-and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNF alpha supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. (C) 2016 Elsevier B.V. All rights reserved.},
  language  = {en}
}
@article{DoegeHoenzkeSchumacheretal.2016,
  author    = {D{\"o}ge, Nadine and H{\"o}nzke, Stefan and Schumacher, Fabian and Balzus, Benjamin and Colombo, Miriam and Hadam, Sabrina and Rancan, Fiorenza and Blume-Peytavi, Ulrike and Sch{\"a}fer-Korting, Monika and Schindler, Anke and R{\"u}hl, Eckart and Skov, Per Stahl and Church, Martin K. and Hedtrich, Sarah and Kleuser, Burkhard and Bodmeier, Roland and Vogt, Annika},
  title     = {Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers},
  series = {Journal of controlled release},
  volume    = {242},
  journal   = {Journal of controlled release},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0168-3659},
  doi       = {10.1016/j.jconrel.2016.07.009},
  pages     = {25 -- 34},
  year      = {2016},
  abstract  = {Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-termex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24 h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05\%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24 h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6 h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45 kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for preclinical assessment of novel drug delivery systems at therapeutic doses in models of diseased skin. (C) 2016 Elsevier B.V. All rights reserved.},
  language  = {en}
}