TY  - JOUR
A1  - Döge, Nadine
A1  - Hönzke, Stefan
A1  - Schumacher, Fabian
A1  - Balzus, Benjamin
A1  - Colombo, Miriam
A1  - Hadam, Sabrina
A1  - Rancan, Fiorenza
A1  - Blume-Peytavi, Ulrike
A1  - Schäfer-Korting, Monika
A1  - Schindler, Anke
A1  - Rühl, Eckart
A1  - Skov, Per Stahl
A1  - Church, Martin K.
A1  - Hedtrich, Sarah
A1  - Kleuser, Burkhard
A1  - Bodmeier, Roland
A1  - Vogt, Annika
T1  - 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
JF  - Journal of controlled release
N2  - 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.
KW  - Drug delivery systems
KW  - Polymeric nanoparticles
KW  - Dexamethasone
KW  - Microdialysis
KW  - Skin penetration
KW  - Skin barrier disruption
Y1  - 2016
U6  - https://doi.org/10.1016/j.jconrel.2016.07.009
SN  - 0168-3659
SN  - 1873-4995
VL  - 242
SP  - 25
EP  - 34
PB  - Elsevier
CY  - Amsterdam
ER  -