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Dive into the research topics where Dominik Selzer is active.

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Featured researches published by Dominik Selzer.


Advanced Drug Delivery Reviews | 2013

Finite and infinite dosing: Difficulties in measurements, evaluations and predictions

Dominik Selzer; Mona M.A. Abdel-Mottaleb; Tsambika Hahn; Ulrich F. Schaefer; Dirk Neumann

Due to the increased demand for reliable data regarding penetration into and permeation across human skin, assessment of the absorption of xenobiotics has been gaining in importance steadily. In vitro experiments allow for determining these data faster and more easily than in vivo experiments. However, the experiments described in literature and the subsequent evaluation procedures differ considerably. Here we will give an overview on typical finite and infinite dose experiments performed in fundamental research and on the evaluation of the data. We will point out possible difficulties that may arise and give a short overview on attempts at predicting skin absorption in vitro and in vivo.


ACS Nano | 2015

Proteomic and Lipidomic Analysis of Nanoparticle Corona upon Contact with Lung Surfactant Reveals Differences in Protein, but Not Lipid Composition.

Simon Sebastian Raesch; Stefan Tenzer; Wiebke Storck; Alexander Rurainski; Dominik Selzer; Christian A. Ruge; Jesús Pérez-Gil; Ulrich F. Schaefer; Claus-Michael Lehr

Pulmonary surfactant (PS) constitutes the first line of host defense in the deep lung. Because of its high content of phospholipids and surfactant specific proteins, the interaction of inhaled nanoparticles (NPs) with the pulmonary surfactant layer is likely to form a corona that is different to the one formed in plasma. Here we present a detailed lipidomic and proteomic analysis of NP corona formation using native porcine surfactant as a model. We analyzed the adsorbed biomolecules in the corona of three NP with different surface properties (PEG-, PLGA-, and Lipid-NP) after incubation with native porcine surfactant. Using label-free shotgun analysis for protein and LC-MS for lipid analysis, we quantitatively determined the corona composition. Our results show a conserved lipid composition in the coronas of all investigated NPs regardless of their surface properties, with only hydrophilic PEG-NPs adsorbing fewer lipids in total. In contrast, the analyzed NP displayed a marked difference in the protein corona, consisting of up to 417 different proteins. Among the proteins showing significant differences between the NP coronas, there was a striking prevalence of molecules with a notoriously high lipid and surface binding, such as, e.g., SP-A, SP-D, DMBT1. Our data indicate that the selective adsorption of proteins mediates the relatively similar lipid pattern in the coronas of different NPs. On the basis of our lipidomic and proteomic analysis, we provide a detailed set of quantitative data on the composition of the surfactant corona formed upon NP inhalation, which is unique and markedly different to the plasma corona.


European Journal of Pharmaceutics and Biopharmaceutics | 2013

Towards drug quantification in human skin with confocal Raman microscopy.

Lutz Franzen; Dominik Selzer; Joachim W. Fluhr; Ulrich F. Schaefer; Maike Windbergs

Understanding the penetration behaviour of drugs into human skin is a prerequisite for the rational development and evaluation of effective dermal drug delivery. The general procedure for the acquisition of quantitative drug penetration profiles in human skin is performed by sequential segmentation and extraction. Unfortunately, this technique is destructive, laborious and lacks spatial resolution. Confocal Raman microscopy bares the potential of a chemically selective, label free and nondestructive analysis. However, the acquisition of quantitative drug depth profiles within skin by Raman microscopy is impeded by imponderable signal attenuation inside the tissue. In this study, we present a chemical semi-solid matrix system simulating the optical properties of human skin. This system serves as a skin surrogate for investigation of Raman signal attenuation under controlled conditions. Caffeine was homogeneously incorporated within the skin surrogate, and Raman intensity depth profiles were acquired. A mathematical algorithm describing the Raman signal attenuation within the surrogate was derived from these profiles. Human skin samples were incubated with caffeine, and Raman intensity depth profiles were similarly acquired. The surrogate algorithm was successfully applied to correct the drug profiles in human skin for signal attenuation. For the first time, a mathematical algorithm was established, which allows correction of Raman signal attenuation in human skin, thus facilitating reliable drug quantification in human skin by confocal Raman spectroscopy.


Journal of Pharmaceutical Sciences | 2011

An Extended Database of Keratin Binding

Steffi Hansen; Dominik Selzer; Ulrich F. Schaefer; Gerald B. Kasting

Diffusion modeling of dermal absorption relies in large part on high quality input data. Currently, estimates of corneocyte-phase partitioning are based on an analysis of a dataset of limited size and diversity. Therefore, we have updated and broadened the analysis. For this purpose, binding coefficients to different keratins, namely, bovine hoof and horn, human delipidized callus, human delipidized stratum corneum (SC), human nail, human hair, and sheep wool were collected from the literature. In addition, binding coefficients to hoof/horn and delipidized SC were measured for eight hydrophilic compounds including three ionizable compounds that were measured at different pH values. Important results are: (i) only hoof/horn, callus, and delipidized SC are suitable keratins for estimating corneocyte protein binding; (ii) binding coefficients to hoof/horn, callus, and delipidized SC can be predicted from the octanol-water partition coefficients log K(o/w) confirming the analysis of the limited dataset; (iii) binding of ionizable compounds can be predicted by correcting log K(o/w) for pH; (iv) the correlation derived for the extended database is steeper than the relationship derived for the limited dataset. This has consequences for the estimates of SC partition and diffusion coefficients for diffusion modeling of dermal absorption. .


Journal of Controlled Release | 2016

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

C. Mathes; A. Melero; P. Conrad; T. Vogt; Lucas Almeida Rigo; Dominik Selzer; Willian Prado; C. De Rossi; T.M. Garrigues; S. Hansen; Guterres Ss; Adriana Raffin Pohlmann; Ruy Carlos Ruver Beck; C.-M. Lehr; Ulrich F. Schaefer

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.


Journal of Controlled Release | 2013

Finite dose skin mass balance including the lateral part: comparison between experiment, pharmacokinetic modeling and diffusion models.

Dominik Selzer; Tsambika Hahn; Arne Naegel; Michael Heisig; Karl-Heinz Kostka; Claus-Michael Lehr; Dirk Neumann; Ulrich F. Schaefer; Gabriel Wittum

This work investigates in vitro finite dose skin absorption of the model compounds flufenamic acid and caffeine experimentally and mathematically. The mass balance in different skin compartments (donor, stratum corneum (SC), deeper skin layers (DSL), lateral skin parts and acceptor) is analyzed as a function of time. For both substances high amounts were found in the lateral skin compartment after 6h of incubation, which emphasizes not to elide these parts in the modeling. Here, three different mathematical models were investigated and tested with the experimental data: a pharmacokinetic model (PK), a detailed microscopic two-dimensional diffusion model (MICRO) and a macroscopic homogenized diffusion model (MACRO). While the PK model was fitted to the experimental data, the MICRO and the MACRO models employed input parameters derived from infinite dose studies to predict the underlying diffusion process. All models could satisfyingly predict or describe the experimental data. The PK model and MACRO model also feature the lateral parts.


Experimental Dermatology | 2012

Influence of the application area on finite dose permeation in relation to drug type applied

Tsambika Hahn; Dominik Selzer; Dirk Neumann; Karl-Heinz Kostka; Claus-Michael Lehr; Ulrich F. Schaefer

Abstract:  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.


Expert Opinion on Drug Metabolism & Toxicology | 2015

Mathematical models for dermal drug absorption

Dominik Selzer; Dirk Neumann; Ulrich F. Schaefer

Introduction: Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approaches has its own virtues and limitations, it may be difficult to decide which approach is best suited to address a given problem. Areas covered: Here we outline the basic ideas, drawbacks and advantages of compartmental and quantitative structure-activity relationship models, as well as of analytical and numerical approaches for solving the diffusion equation. Examples of special applications of the different approaches are given. Expert opinion: Although some models are sophisticated and might be used in future to predict transport through damaged or diseased skin, the comparatively low availability of suitable and accurate experimental data limits extensive usage of these models and their predictive accuracy. Due to the lack of experimental data, the possibility of validating mathematical models is limited.


European Journal of Pharmaceutics and Biopharmaceutics | 2015

A strategy for in-silico prediction of skin absorption in man

Dominik Selzer; Dirk Neumann; Heike Neumann; Karl-Heinz Kostka; Claus-Michael Lehr; Ulrich F. Schaefer

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.


Archive | 2017

Human Native and Reconstructed Skin Preparations for In Vitro Penetration and Permeation Studies

Ulrich F. Schaefer; Dominik Selzer; Steffi Hansen; Claus-Michael Lehr

In vitro skin absorption studies are essential for dermal product development as well as in dermal risk assessment. This chapter introduces commonly used membranes for permeation and penetration studies, such as from human, animal, bioengineered, or artificial sources. In addition two basic types of experiments to investigate transdermal solute transport are discussed. In permeation studies, the substance transport through the skin is evaluated and systemic availability is addressed. In contrast penetration studies gain information on substance distribution in different skin layers, allowing the identification of substance depots in various skin layers. Furthermore, basic experimental setups for skin transport studies are addressed, e.g., finite and infinite dosing, vertical and horizontal diffusion cells, and static versus flow-through cells. Furthermore, the influence of fundamental experimental conditions on diffusion experiments, such as the choice of acceptor solution and temperature, are discussed.

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Arne Naegel

Goethe University Frankfurt

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