TY - JOUR A1 - Hönzke, Stefan A1 - Gerecke, Christian A1 - Elpelt, Anja A1 - Zhang, Nan A1 - Unbehauen, Michael A1 - Kral, Vivian A1 - Fleige, Emanuel A1 - Paulus, Florian A1 - Haag, Rainer A1 - Schäfer-Korting, Monika A1 - Kleuser, Burkhard A1 - Hedtrich, Sarah T1 - Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing JF - Journal of controlled release N2 - 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. KW - Dendritic core-multishell nanocarriers KW - Biocompatibility KW - Dexamethasone KW - Inflammatory skin disease KW - Dermal drug delivery KW - Skin model Y1 - 2016 U6 - https://doi.org/10.1016/j.jconrel.2016.06.030 SN - 0168-3659 SN - 1873-4995 VL - 242 SP - 50 EP - 63 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Han, Xiao Xia A1 - Li, Junbo A1 - Öner, Ibrahim Halil A1 - Zhao, Bing A1 - Leimkühler, Silke A1 - Hildebrandt, Peter A1 - Weidinger, Inez M. T1 - Nickel electrodes as a cheap and versatile platform for studying structure and function of immobilized redox proteins JF - Analytica chimica acta : an international journal devoted to all branches of analytical chemistry N2 - Practical use of many bioelectronic and bioanalytical devices is limited by the need of expensive materials and time consuming fabrication. Here we demonstrate the use of nickel electrodes as a simple and cheap solid support material for bioelectronic applications. The naturally nanostructured electrodes showed a surprisingly high electromagnetic surface enhancement upon light illumination such that immobilization and electron transfer reactions of the model redox proteins cytochrome b(5) (Cyt b(5)) and cytochrome c (Cyt c) could be followed via surface enhanced resonance Raman spectroscopy. It could be shown that the nickel surface, when used as received, promotes a very efficient binding of the proteins upon preservation of their native structure. The immobilized redox proteins could efficiently exchange electrons with the electrode and could even act as an electron relay between the electrode and solubilized myoglobin. Our results open up new possibility for nickel electrodes as an exceptional good support for bioelectronic devices and biosensors on the one hand and for surface enhanced spectroscopic investigations on the other hand. (C) 2016 Elsevier B.V. All rights reserved. KW - Ni electrodes KW - Redox proteins KW - Surface enhanced Raman spectroscopy KW - Electron relay KW - Biocompatibility KW - Electron transfer Y1 - 2016 U6 - https://doi.org/10.1016/j.aca.2016.08.053 SN - 0003-2670 SN - 1873-4324 VL - 941 SP - 35 EP - 40 PB - Elsevier CY - Amsterdam ER -