TY  - GEN
A1  - Radbruch, Moritz
A1  - Pischon, Hannah
A1  - Ostrowski, Anja
A1  - Volz, Pierre
A1  - Brodwolf, Robert
A1  - Neumann, Falko
A1  - Unbehauen, Michael
A1  - Kleuser, Burkhard
A1  - Haag, Rainer
A1  - Ma, Nan
A1  - Alexiev, Ulrike
A1  - Mundhenk, Lars
A1  - Gruber, Achim D.
T1  - Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin
T2  - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe
N2  - Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e. g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.

Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection.

Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis.

Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 724 
KW  - CMS
KW  - skin
KW  - topical treatment
KW  - dermal delivery
KW  - atopic dermatitis
KW  - oxazolone
KW  - fluorescence lifetime imaging microscopy
KW  - nanomaterials
KW  - multi-domain nanoparticles
KW  - penetration enhancement
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-430136
SN  - 1866-8372
IS  - 724
ER  - 
TY  - GEN
A1  - Prüfer, Nicole
A1  - Kleuser, Burkhard
A1  - van der Giet, Markus
T1  - The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
N2  - The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL’s anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL’s protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL’s biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 340 
KW  - atherosclerosis
KW  - high-density lipoprotein (HDL)
KW  - inflammation
KW  - serum amyloid A (SAA)
KW  - sphingosine-1-phosphate (S1P)
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-398648
ER  -