Christian Zoschke

Freie Universität Berlin | FUB · Pharmacology

Sensitive mapping of drugs and drug delivery systems is pivotal for the understanding and improvement of treatment options. Since labeling alters the physicochemical and potentially the pharmacological properties of the...

The improved understanding of disease pathways enables the identification of relevant pharmacological targets and the development of drugs addressing these targets. Although a great deal of the focus for active targeted nanotechnology has been on anti-cancer drugs, the need for active targeting nanotechnology and the same translational gap applies...

The increasing number of tattooed persons urges the development of reliable test systems to assess tattoo associated risks. The alarming prevalence of 60% phototoxic reactions in tattoos ask for a more comprehensive investigation of phototoxic reactions in tattooed skin. Here, we aimed to compare the cellular responses of human skin cells to ultrav...

A plethora of micro- and nanoparticle types are currently investigated for advanced ocular treatment due to improved drug retention times, higher bioavailability and better biocompatibility. Yet, comparative studies of both physicochemical and toxicological performance of these novel drug delivery systems are still rare. Herein, poly(L-lactic acid)...

3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main disadvantages of the matrices commonly used for in...

Preclinical research struggles with its predictive power for drug effects in patients. The clinical success of preclinically approved drug candidates ranges between 3% and 33%. Regardless of the approach, novel disease models and test methods need to prove their relevance and reliability for predicting drug effects in patients, which is usually ach...

Pharmacotherapy of head and neck squamous cell carcinoma (HNSCC) often fails due to the development of chemoresistance and severe systemic side effects of current regimens limiting dose escalation. Preclinical models comprising all major elements of treatment resistance are urgently needed for the development of new strategies to overcome these lim...

Skin model cultivation under static conditions limits the observation of the toxicity to this single organ. Biology-inspired microphysiological systems associating skin with a liver in the same circulating medium provide a more comprehensive insight into systemic substance toxicity; however, its advantages or limitations for topical substance toxic...

Reports of tattoo-associated risks boosted the interest in tattoo pigment toxicity over the last decades. Nonetheless, the influence of tattoo pigments on skin homeostasis remains largely unknown. In vitro systems are not available to investigate the interactions between pigments and skin. Here, we established TatS, a reconstructed human full-thick...

Fluorescence microscopy is widely used for high content screening in 2D cell cultures and 3D models. In particular, 3D tissue models are gaining major relevance in modern drug development. Enabling direct multiparametric evaluation of complex samples, fluorescence lifetime imaging (FLIM) adds a further level to intensity imaging by the sensitivity...

Cancer treatment often lacks individual dose adaptation, contributing to insufficient efficacy and severe side effects. Thus, personalized approaches are highly desired. Although various analytical techniques are established to determine drug levels in preclinical models, they are limited in the automated real-time acquisition of pharmacokinetic pr...

UV light catalyzes the ozone formation from air pollutants, like nitrogen oxides. Since ozone reacts with cutaneous sebum lipids to peroxides and, thus, promotes inflammation, tumorigenesis, and aging, even broad-spectrum sunscreens cannot properly protect skin. Meanwhile, xanthophylls, like fucoxanthin, proved their antioxidant and cytoprotective...

Age-related changes affect both the local pharmacotherapy of skin diseases and the transdermal administration of drugs. The development of aged skin models disregards the highly individual process of aging, facilitating general conclusions for older patients. Nevertheless, 'omics technology, high-content screening, and non-invasive imaging, as well...

Numerous studies have employed tape stripping (TS) or cyanoacrylate stripping (CS) to induce skin barrier disruption of the stratum corneum (SC) in human and porcine skin. However, the thickness of the remaining SC and the respective changes of the skin permeability have been rarely quantified. By using high-resolution multiphoton tomography, about...

Recent studies using 3D scaffolds have emphasized the importance of the surrounding stroma on chemoresistance in drug efficacy screenings. Since 15-lipoxygenase (15-LOX) metabolites reduced growth of breast, colon, prostate, lung and leukemia cancer cells in 2D cell culture, we were intrigued by the direct comparison of 15-LOX metabolite efficacy i...

Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed chitosan–heparin nanoparticles by a one-step process...

Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morpho...

Background/aims: The skin provides protection against chemical, physical, and biological stressors, yet the skin morphology changes over the course of life. These changes might affect the skin barrier function and facilitate the onset of age-related diseases. Since orally applied lactic acid bacteria ameliorate signs of aged and atopic skin, we in...

Preclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts d...

Aging depicts one of the major challenges in pharmacology owing to its complexity and heterogeneity. Thereby, advanced glycated end-products modify extracellular matrix proteins, but the consequences on the skin barrier function remain heavily understudied. Herein, we utilized transmission electron microscopy for the ultrastructural analysis of rib...

Human cell-based approaches to assess defined key events in allergic contact dermatitis (ACD) are well-established, but lack cutaneous penetration and biotransformation as well as cellular cross-talk. Herein, we integrated in vitro-generated immature MUTZ-3-derived Langerhans-like cells (MUTZ-LCs) or monocyte-derived LC-like cells (MoLCs) into reco...

We report here on a custom-built time-correlated single photon-counting (TCSPC)-based fluorescence lifetime imaging microscopy (FLIM) setup with a continuously tunable white-light supercontinuum laser combined with acousto-optical tunable filters (AOTF) as an excitation source for simultaneous excitation of multiple spectrally separated fluorophore...

Targeted topical application promises high drug concentrations in the skin and low systemic adverse effects. To locate drugs and drug-delivery systems like nanocarriers, fluorescent dyes are commonly used as drug surrogates or nanocarrier labels in micrographs of tissue sections. Here, we investigate how labeling degree, concentration of fluorophor...

Extrinsic (photo) aging accelerates chronologically aging in the skin due to cumulative UV irradiation. Despite recent insights into the molecular mechanisms of fibroblast aging, age-related changes of the skin barrier function have been understudied. In contrast, the constantly increasing subpopulation of aged patients causes a clinical need for e...

Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While th...

The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parame...

Dendritic nanoparticles have been developed with auspicious propertieslike high loading capacity for guest molecules, low polydispersity and tunable end groups. Demonstrating increased cellular uptake, and bypassed efflux transporters,dendritic nanoparticles may offer new treatment options for therapy-resistant diseases. New core-shell architecture...

A growing intended or accidentally exposure to nanoparticles asks for the elucidation of potential toxicity linked to the penetration of normal and lesional skin. We studied the skin penetration of dye-tagged dendritic core-multishell (CMS) nanotransporters and of Nile red loaded CMS nanotransporters using fluorescence microscopy. Normal and stripp...

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin pene...

The modes of drug-particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well...