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Lebach, Germany

Labouta H.I.,Saarland University | Labouta H.I.,Alexandria University | Hampel M.,Fraunhofer Institute for Interfacial Engineering and Biotechnology | Thude S.,Fraunhofer Institute for Interfacial Engineering and Biotechnology | And 3 more authors.
Journal of Biophotonics | Year: 2012

Multiphoton microscopy has become popular in studying dermal nanoparticle penetration. This necessitates studying the imaging parameters of multiphoton microscopy in skin as an imaging medium, in terms of achievable detection depths and the resolution limit. This would simulate real-case scenarios rather than depending on theoretical values determined under ideal conditions. This study has focused on depth profiling of sub-resolution gold nanoparticles (AuNP) in reconstructed (fixed and unfixed) and human skin using multiphoton microscopy. Point spread functions (PSF) were determined for the used water-immersion objective of 63×/NA = 1.2. Factors such as skin-tissue compactness and the presence of wrinkles were found to deteriorate the accuracy of depth profiling. A broad range of AuNP detectable depths (20-100 μm) in reconstructed skin was observed. AuNP could only be detected up to ~14 μm depth in human skin. Lateral (0.5 ± 0.1 μm) and axial (1.0 ± 0.3 μm) PSF in reconstructed and human specimens were determined. Skin cells and intercellular components didn't degrade the PSF with depth. In summary, the imaging parameters of multiphoton microscopy in skin and practical limitations encountered in tracking nanoparticle penetration using this approach were investigated. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hahn T.,Saarland University | Selzer D.,Saarland University | Neumann D.,Saarland University | Kostka K.-H.,Caritaskrankenhaus | And 3 more authors.
Experimental Dermatology | Year: 2012

For finite dose skin absorption experiments, a homogeneous donor distribution over the skin surface is usually assumed. However, the influence of the surface distribution on skin absorption is still unknown. The aim of this study was to evaluate the influence of the application area on the permeation of drugs during finite dose skin absorption experiments in static Franz diffusion cells. Permeation experiments with stained aqueous drug formulations were conducted, and the application area was determined by a suitable, objective, automated computational approach. The permeation of caffeine is strongly dependent on the application area. The variability between single experiments decreased when including the application area. For the lipophilic flufenamic acid, this was not the case. The variability highly increased after inclusion of the application area. Thus, a correction of the area is misleading. In summary, depending on the drug's physicochemical characteristics, the application area may influence skin absorption. © 2011 John Wiley & Sons A/S.


Selzer D.,Saarland University | Neumann D.,Saarland University | Neumann H.,Saarland University | Kostka K.-H.,Caritaskrankenhaus | And 3 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2015

For some time, in-silico models to address substance transport into and through the skin are gaining more and more importance in different fields of science and industry. In particular, the mathematical prediction of in-vivo skin absorption is of great interest to overcome ethical and economical issues. The presented work outlines a strategy to address this problem and in particular, investigates in-vitro and in-vivo skin penetration experiments of the model compound flufenamic acid solved in an ointment by means of a mathematical model. Experimental stratum corneum concentration-depth profiles (SC-CDP) for various time intervals using two different in-vitro systems (Franz diffusion cell, Saarbruecken penetration model) were examined and simulated with the help of a highly optimized three compartment numerical diffusion model and compared to the findings of SC-CDPs of the in-vivo scenario. Fitted model input parameters (diffusion coefficient and partition coefficient with respect to the stratum corneum) for the in-vitro infinite dose case could be used to predict the in-use conditions in-vitro. Despite apparent differences in calculated partition coefficients between in-vivo and in-vitro studies, prediction of in-vivo scenarios from input parameters calculated from the in-vitro case yielded reasonable results. © 2015 Elsevier B.V. All rights reserved.


Hahn T.,Saarland University | Hansen S.,Saarland University | Neumann D.,Saarland University | Kostka K.-H.,Caritaskrankenhaus | And 3 more authors.
Skin Pharmacology and Physiology | Year: 2010

The investigation of drug penetration into the stratum corneum (SC) by tape-stripping requires an accurate measure of the amount of SC on each tape-strip in order to determine the depth inside the SC. This study applies infrared densitometry (IR-D) to in vitro tape-stripping using the novel Squame Scan® 850A. The device had recently been shown to provide accurate measurements of the SC depth for tape-stripping in vivo. Furthermore, the suitability of IR-D for determining the endpoint of tape-stripping, i.e. complete SC removal, was tested. The SC depth was computed from the IR-D data of sequential tape-strips and compared to the results of a protein assay as gold standard. IR-D provided accurate depth results both for freshly excised skin and for skin stored frozen for up to 3 months. In addition, the lower limit of quantification of IR-D indicates the complete removal of the SC (less than 5% of the total SC remaining) and can be used for adjusting the number of tapes applied in situ. Therefore, IR-D is an accurate, fast and non-destructive method for SC depth determination. © 2010 S. Karger AG, Basel.


Franzen L.,Saarland University | Anderski J.,Saarland University | Planz V.,Saarland University | Planz V.,PharmBioTec GmbH | And 4 more authors.
Experimental Dermatology | Year: 2014

In the area of dermatological research, the knowledge of rate and extent of substance penetration into the human skin is essential not only for evaluation of therapeutics, but also for risk assessment of chemicals and cosmetic ingredients. Recently, confocal Raman microscopy emerged as a novel analytical technique for analysis of substance skin penetration. In contrast to destructive drug extraction and quantification, the technique is non-destructive and provides high spatial resolution in three dimensions. However, the generation of time-resolved concentration depth profiles is restrained by ongoing diffusion of the penetrating substance during analysis. To prevent that, substance diffusion in excised human skin can instantly be stopped at defined time points by freeze-drying the sample. Thus, combining sample preparation by freeze-drying with drug quantification by confocal Raman microscopy yields a novel analytical platform for non-invasive and quantitative in vitro analysis of substance skin penetration. This work presents the first proof-of-concept study for non-invasive quantitative substance depth profiling in freeze-dried excised human stratum corneum by confocal Raman microscopy. © 2014 John Wiley & Sons A/S.

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