TY  - JOUR
A1  - Edlich, Alexander
A1  - Volz, Pierre
A1  - Brodwolf, Robert
A1  - Unbehauen, Michael
A1  - Mundhenk, Lars
A1  - Gruber, Achim D.
A1  - Hedtrich, Sarah
A1  - Haag, Rainer
A1  - Alexiev, Ulrike
A1  - Kleuser, Burkhard
T1  - Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin
JF  - Biomaterials : biomaterials reviews online
N2  - Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment. (C) 2018 Elsevier Ltd. All rights reserved.
KW  - Core-multishell nanocarriers
KW  - Fluorescence lifetime imaging microscopy
KW  - Langerhans cells
KW  - Nanoparticle uptake
KW  - Nanotoxicology
Y1  - 2018
U6  - https://doi.org/10.1016/j.biomaterials.2018.01.058
SN  - 0142-9612
SN  - 1878-5905
VL  - 162
SP  - 60
EP  - 70
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - GEN
A1  - Pischon, Hannah
A1  - Radbruch, Moritz
A1  - Ostrowski, Anja
A1  - Schumacher, Fabian
A1  - Hoenzke, Stefan
A1  - Kleuser, Burkhard
A1  - Hedtrich, Sarah
A1  - Fluhr, Joachim W.
A1  - Gruber, Achim D.
A1  - Mundhenk, Lars
T1  - How Effective Is Tacrolimus in the Imiquimod
BT  - Induced Mouse Model of Psoriasis?
T2  - The journal of investigative dermatology
Y1  - 2017
U6  - https://doi.org/10.1016/j.jid.2017.09.019
SN  - 0022-202X
SN  - 1523-1747
VL  - 138
IS  - 2
SP  - 455
EP  - 458
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Radbruch, Moritz Jan Florian
A1  - Pischon, Jeanette Hannah Charlotte
A1  - Du, Fang
A1  - Haag, Rainer
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Mundhenk, Lars
A1  - Gruber, Achim
T1  - Biodegradable core-multishell nanocarrier: topical tacrolimus delivery for treatment of dermatitis
JF  - Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems
N2  - Two challenges in topical drug delivery to the skin include solubilizing hydrophobic drugs in water-based formulations and increasing drug penetration into the skin. Polymeric core-multishell nanocarrier (CMS), particularly the novel biodegradable CMS (bCMS = hPG-PCL1.1K-mPEG(2k)-CMS) have shown both advantages on excised skin ex vivo. 
Here, we investigated topical delivery of tacrolimus (TAC; > 500 g/mol) by bCMS in a hydrogel on an oxazolone-induced model of dermatitis in vivo. As expected, bCMS successfully delivered TAC into the skin. 
However, in vivo they did not increase, but decrease TAC penetration through the stratum corneum compared to ointment. 
Differences in the resulting mean concentrations were mostly non-significant in the skin (epidermis: 35.7 +/- 20.9 ng/cm(2) for bCMS vs. 92.6 +/- 62.7 ng/cm(2) for ointment; dermis: 76.8 +/- 26.8 ng/cm(2) vs 118.2 +/- 50.4 ng/cm(2)), but highly significant in blood (plasma: 1.1 +/- 0.4 ng/ml vs 11.3 +/- 9.3 ng/ml; erythrocytes: 0.5 +/- 0.2 ng/ml vs 3.4 +/- 2.4 ng/ml) and liver (0.01 +/- 0.01 ng/mg vs 0.03 +/- 0.01 ng/mg). bCMS were detected in the stratum corneum but not in viable skin or beyond. 
The therapeutic efficacy of TAC delivered by bCMS was equivalent to that of standard TAC ointment. 
Our results suggest that bCMS may be a promising carrier for the topical delivery of TAC. The quantitative difference to previous results should be interpreted in light of structural differences between murine and human skin, but highlights the need as well as potential methods to develop more a complex ex vivo analysis on human skin to ensure quantitative predictive value.
KW  - drug delivery systems
KW  - core-multishell (CMS) nanocarriers
KW  - tacrolimus
KW  - topical drug delivery
KW  - dermal drug administration
KW  - penetration enhancement
Y1  - 2022
U6  - https://doi.org/10.1016/j.jconrel.2022.07.025
SN  - 0168-3659
SN  - 1873-4995
VL  - 349
SP  - 917
EP  - 928
PB  - Elsevier
CY  - New York, NY [u.a.]
ER  -