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

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• 作者：Nadine Dö ; ge^a ; ^b ; ^{nadine.doege@charite.de" class="auth_mail" title="E-mail the corresponding author} ; Stefan Hö ; nzke^b ; ^{stefan.hoenzke@fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Fabian Schumacher^c ; ^d ; ^{fabian.schumacher@uni-potsdam.de" class="auth_mail" title="E-mail the corresponding author} ; Benjamin Balzus^e ; ^{balzus@zedat.fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Miriam Colombo^e ; ^{mcolombo@zedat.fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Sabrina Hadam^a ; ^{sabrina.hadam@charite.de" class="auth_mail" title="E-mail the corresponding author} ; Fiorenza Rancan^a ; ^{fiorenza.rancan@charite.de" class="auth_mail" title="E-mail the corresponding author} ; Ulrike Blume-Peytavi^a ; ^{ulrike.blume-peytavi@charite.de" class="auth_mail" title="E-mail the corresponding author} ; Monika Schä ; fer-Korting^b ; ^{monika.schaefer-korting@fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Anke Schindler^f ; ^{anke.schindler@fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Eckart Rü ; hl^f ; ^{ruehl@zedat.fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Per Stahl Skov^g ; ^h ; ^{pss@reflab.dk" class="auth_mail" title="E-mail the corresponding author} ; Martin K. Church^h ; ^{M.K.Church@soton.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Sarah Hedtrich^b ; ^{sarah.hedtrich@fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Burkhard Kleuser^c ; ^{kleuser@uni-potsdam.de" class="auth_mail" title="E-mail the corresponding author} ; Roland Bodmeier^e ; ^{bodmeier@zedat.fu-berlin.de" class="auth_mail" title="E-mail the corresponding author} ; Annika Vogt^a ; ^{annika.vogt@charite.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CSSS ; cyanoacrylate skin surface stripping ; Dex ; dexamethasone ; FE-SEM ; field emission scanning electron microscope ; HPLC ; high performance liquid chromatography ; IL ; interleukin ; LC-MS/MS ; liquid-chromatography &ndash ; tandem-mass spectrometry ; OCT ; optical coherent tomography ; PBS ; phosphate buffered saline ; PDI ; polydispersity index ; PVA ; polyvinyl alcohol ; SLS ; sodium lauryl sulfate ; TEWL ; transepidermal water loss
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 November 2016
• 年：2016
• 卷：242
• 期：Complete
• 页码：25-34
• 全文大小：1423 K

文摘

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-term ex 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.