Across Barriers GmbH

Saarbrücken, Germany

Across Barriers GmbH

Saarbrücken, Germany
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PubMed | BASF, TU Berlin, University of South Australia, Epithelix Sarl and 16 more.
Type: Journal Article | Journal: ALTEX | Year: 2015

Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.


Brinkmann J.,German Federal Institute for Risk Assessment | Stolpmann K.,German Federal Institute for Risk Assessment | Trappe S.,German Federal Institute for Risk Assessment | Otter T.,German Federal Institute for Risk Assessment | And 6 more authors.
Toxicological Sciences | Year: 2013

The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is metabolized into a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE) is formed to certain extents. Skin is frequently in contact with PAHs and data on the metabolic capacity of skin tissue toward these compounds are inconclusive. We compared BP metabolism in excised human skin, commercially available in vitro 3D skin models and primary 2D skin cell cultures, and analyzed the metabolically catalyzed occurrence of seven different BP follow-up products by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). All models investigated were competent to metabolize BP, and the metabolic profiles generated by ex vivo human skin and skin models were remarkably similar. Furthermore, the genotoxicity of BP and its derivatives was monitored in these models via comet assays. In a full-thickness skin, equivalent BP-mediated genotoxic stress was generated via keratinocytes. Cultured primary keratinocytes revealed a level of genotoxicity comparable with that of direct exposure to 50-100nM of BPDE. Our data demonstrate that the metabolic capacity of human skin ex vivo, as well as organotypic human 3D skin models toward BP, is sufficient to cause significant genotoxic stress and thus cutaneous bioactivation may potentially contribute to mutations that ultimately lead to skin cancer. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


Kiessling H.,University of Tübingen | Schulz I.,Microfluidic ChipShop GmbH | Haltner E.,Across Barriers GmbH | Fricker G.,University of Heidelberg | And 2 more authors.
BioSpektrum | Year: 2015

State of the art animal and cell culture models fail to predict the ability of drugs to cross the blood-brain barrier as they lack comparability to the complex human situation. The development of novel pharmaceutics therefore requires in vitro models with human like cell response. Therefore, we are developing a model which mimics the organ environment including the specific 3D arrangement of different cell types, extracellular matrix, and perfusion by combining biology, biochemistry and microfluidic technology. © 2015, Springer-Verlag Berlin Heidelberg.


Kiessling H.,University of Tübingen | Becker H.,Microfluidic ChipShop GmbH | Haltner E.,Across Barriers GmbH | Schutte J.,University of Tübingen | And 4 more authors.
MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences | Year: 2015

Development of novel drugs for indication in the central nervous system often fails due to the inability of most substances to cross the blood-brain barrier. State of the art animal and cell culture models fail to predict a substance's ability to cross this barrier as they lack comparability to the complex human situation. Therefore, we are developing a model which mimics the organ environment including the specific 3D arrangement of different cell types, extracellular matrix, and perfusion by combining biology, biochemistry and microfluidic technology. In this paper we present a microfluidic device modelling the blood-brain barrier, using dielectrophoretic forces for cell assembly. © 15CBMS-0001.


Eixarch H.,Across Barriers GmbH | Haltner-Ukomadu E.,Across Barriers GmbH | Beisswenger C.,Across Barriers GmbH | Bock U.,Across Barriers GmbH
Journal of Epithelial Biology and Pharmacology | Year: 2010

The respiratory tract is currently considered as an alternative to gastrointestinal and dermal drug delivery systems and is used to deliver drugs for respiratory diseases as well as the treatment of non-pulmonary disorders. The first step in drug profiling for delivery via the respiratory tract needs to address intrinsic physicochemical parameters and their impact on or correlation with absorption. Moreover, the more the pulmonary drug delivery shall find acceptance, the greater will be the need for validated test systems, methods, and guidelines for regulatory purposes. The Biopharmaceutical Classification System (BCS) remains the simplest and most common guiding principle for predicting drug absorption, but it is limited to the gastrointestinal tract. This review suggests an extension, the pulmonary Biopharmaceutical Classification System (pBCS), that will take into consideration the specific biology of the lung as well as particle deposition, aerosol physics, and the subsequent processes of drug absorption and solubility. We will describe the steps to be taken to develop a pBCS as well as the compounds that will be used to establish this classification. Furthermore, we will introduce two cellular models with which drug permeability across the pulmonary barrier will be determined as an alternative to the currently and widely used studies with animals. © Eixarch et al.

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