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201
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Introduction
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August 2013 - present
Publications
Publications (201)
The topical application of drug-loaded particles has been explored extensively aiming at a dermal, follicular or transdermal drug delivery. This review summarizes the present state of the field of polymeric nanocarriers for skin application, also covering methodologies to clinically characterize their interaction and penetration in skin in vivo. Fu...
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.
Label-free detection of core-multishell (CMS) nanocarriers and the anti-inflammatory drug dexamethasone is reported. Selective excitation by tunable soft X-rays in the O 1s-regime is used for probing either the CMS nanocarrier or the drug. Furthermore, the drug loading efficiency into CMS nanocarriers is determined by X-ray spectroscopy. The drug-l...
Transcutaneous immunization (TCI) requires targeting of a maximum number of skin antigen-presenting cells as non-invasive as possible on small skin areas. In two clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS procedure removed only 30%...
Scanning Transmission X‐ray microscopy (STXM) is a sensitive and selective probe for the penetration of rapamycin which is topically applied to human skin ex vivo and is facilitated by skin treatment with microneedles puncturing the skin. Inner‐shell excitation serves as a selective probe for detecting rapamycin by changes in optical density as wel...
Background and Aims
Skin aging is associated with dry skin and a decrease of the strength of the dermoepidermal adhesion, which increases the risk for lacerations (skin tears). Application of leave‐on products improves dry skin and seems to reduce skin tear incidence. The aim of this study was to measure the effects of a humectant containing leave‐...
Importance
Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact.
Objective
To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI).
Evidence Review
A...
Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflamma...
Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human sk...
Citation: Rancan, F.; Jurisch, J.; Hadam, S.; Vogt, A.; Blume-Peytavi, U.; Bayer, I.S.; Contardi, M.; Schaudinn, C. Ciprofloxacin-Loaded Polyvinylpyrrolidone Foils for the Topical Treatment of Wound Infections with Methicillin-Resistant Staphylococcus aureus (MRSA). Abstract: Bacterial infections are a constant challenge in the management of acute...
Zusammenfassung
Rheumatologische Erkrankungen können sich in einer großen Vielfalt an der Haut manifestieren. Das Spektrum reicht von flüchtigen Exanthemen bis zu tiefer Sklerosierung, Vaskulitis und Pannikulitis. Dank der Zugänglichkeit für Inspektion, Dermatoskopie, Palpation und Biopsien können dermatologische Mitbeurteilungen wertvolle Hinweise...
Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172 g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocar...
Alopecia areata (AA) is an autoimmune‐mediated non‐scarring hair loss whose stigmatizing effect may have severe psychosocial impact. AA has been reported to be correlated with bullying, reduced quality of life (QoL) and psychiatric comorbidities. The effect of AA on QoL in adult patients has been systematically reviewed and found to be detrimental....
Since biocatalysts manoeuvre most of the physiological activities in living organisms and exhibit extreme selectivity and specificity, their use to trigger physicochemical change in polymeric architectures has been successfully used for targeted drug delivery. Our major interest is to develop lipase responsive nanoscale delivery systems from bio-co...
The number of patients presenting with frontal fibrosing alopecia (FAA) is increasing not only in hair clinics. The recognition of the peculiar clinical pattern and associated symptoms is an important prerequisite to ensure adequate counseling and therapeutic management of the patients. Experimental studies and a range of case series give first ins...
Adult stem cells have been extensively investigated for tissue repair therapies. Adipose-derived stem cells (ASCs) were shown to improve wound healing by promoting re-epithelialization and vascularization as well as modulating the inflammatory immune response. In this study, we used ex vivo human skin cultured in a six-well plate with trans-well in...
Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute or chronic non-scarring hair loss, with a heterogeneity in clinical manifestations ranging from patchy hair loss to complete scalp and body hair loss. An overview of the up-to-date pathophysiology and the underlying signaling pathways involved in AA together with diag...
Zusammenfassung
Die Alopecia areata (AA) ist eine chronische immunvermittelte Erkrankung, die durch akuten oder chronischen, nicht vernarbenden Haarausfall gekennzeichnet ist. Die klinischen Erscheinungsformen sind sehr unterschiedlich und reichen von kleinen umschriebenen haarlosen Stellen bis hin zum vollständigen Verlust der Kopf- und Körperbeha...
Background
Xerosis cutis or dry skin is a highly prevalent dermatological disorder especially in the elderly and in patients with underlying health conditions. In the past decades, numerous molecular markers have been investigated for their association with the occurrence or severity of skin dryness. The aim of this review was to summarize the mole...
Introduction:
Hair disorders are one of the most common conditions within dermatology practice but, although new diagnostic tools and therapeutic options have arisen, the management of these patients still represents a major clinical challenge.
Objective:
This study aimed at gathering information and achieving consensus on relevant recommendatio...
Introduction
Rapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa sk...
Topical wound management is often a challenge due to the poor penetration of antimicrobials in wound tissue and across the biofilm matrix where bacteria are embedded. Surfactants have been used for decades to improve the stability of formulations, increase drug solubility, and enhance penetration. In this study, we screened different detergents wit...
Background
Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide, but lacks clear aetiology and robust clinical trial evidence for efficacy and safety of agents currently used for treatment.
Objectives
To enable data to be collected worldwide on FFA using common criteria and assessment methods....
Background and objectives:
Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist setmelanotide in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During t...
Pressure ulcers/injuries are caused by sustained loading and deformation of skin and underlying soft tissues. Prophylactic dressings are recommended as an adjunct to other preventive measures such as repositioning and offloading. The aim of this study was to investigate the effects of prophylactic soft silicone multi‐layered foam dressings on the s...
Drug penetration in human skin ex vivo following a modification of skin barrier permeability is systematically investigated by scanning transmission X-ray microscopy. Element-selective excitation is used in the O 1s regime for probing quantitatively the penetration of topically applied rapamycin in different formulations with a spatial resolution r...
A synthetic route for oxidation-sensitive core-multishell (osCMS) nanocarriers was established, and their drug loading and release properties were analyzed based on their structural variations. The nanocarriers showed a drug loading of 0.3-3 wt % for the anti-inflammatory drugs rapamycin and dexamethasone and the photosensitizer meso-tetra-hydroxyp...
Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this explorator...
Importance:
A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata.
Objective:
To generate core domains and domain items...
Importance: A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. Objective: To generate core domains and domain items fo...
Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses by controlling the local inflammatory milieu, the breakdown of which can result in chronic...
Background:
The upper follicular compartment, a well-known reservoir of cutaneous microbiota, constitutes a space for intensive cross-barrier dialogue. The lower follicle comprises the bulb and bulge, structures with relative immune-privileged status, crucial for physiological cycling, and widely considered to be microbial-free.
Objectives:
Foll...
Among polymeric nanocarriers, nanogels are especially promising non-irritating delivery vehicles to increase dermal bioavailability of therapeutics. However, accurately tailoring defined interactions with the amphiphilic skin barrier is still challenging. To address this limited specificity, we herein present a new strategy to combine biocompatible...
A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carb...
Evidence suggests that preventive dressings applied on sacral skin help to prevent pressure ulcers. However, possible performance differences of different dressing types are unclear. An exploratory randomized crossover trial with intra‐individual comparisons was conducted to compare the effects of three different multi‐layer foam dressings (Mepilex...
We report on a congenital tumor of the face and scalp in a male newborn, histologically proven to contain melanocytes, cartilage, and bone, vascular, and neural tissue as part of a pigmented congenital tumor. Thus, this tumor was classified as a cutaneous cephalic neurocristic hamartoma.
Background
Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.
Methods
In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-...
The anatomy of the hair follicle and the dynamics of its barrier provide a special space for interactions between macromolecules and the underlying tissue. Translocation across the hair follicle epithelium and immune recognition have been confirmed for proteins, nucleic acids, engineered particles, virus particles and others. Tissue responses can b...
Background:
We previously reported The Alopecia Areata Consensus of Experts (ACE) Study: Results of an International Expert Opinion on Treatments for Alopecia Areata (AA).
Objective:
To report the results of the ACE international expert opinion on diagnosis and laboratory evaluation for AA.
Methods:
Fifty hair experts from 5 continents were in...
Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine p...
The use of penetration enhancers (chemical or physical) has been proven to dramatically improve the penetration of therapeu-tics. Nevertheless, their use poses great risks, as they can lead to permanent damage on the skin, reducing its barrier efficien-cy and resulting in the intrusion of harmful substances. Among the most used skin penetration enh...
Background
A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high quality randomized controlled trials (RCTs).
Objective
To produce an international consensus statement on the use and utility of various treatments for AA.
Methods
Fifty hair experts from 5 contin...
The skin plays a crucial role in host defences against microbial attack and the innate cells must provide the immune system with sufficient information to organize these defences. This unique feature makes the skin a promising site for vaccine administration. Although cellular innate immune events during vaccination have been widely studied, initia...
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...
Introduction:
Felix Pinkus' concept of the vitreous membrane (VM) published in 1927 describes circular folds protruding into the outer root sheath (ORS), which, in his opinion, serve as interdigitations between the outer root sheath (ORS) and the VM. This concept currently seems to have fallen into oblivion.
Objective:
To determine the origin an...
Previous studies have shown targeting different tissues via the transcutaneous (TC) and intramuscular injection (IM) with or without electroporation (EP) has the potential to trigger immune responses to DNA vaccination. The CUTHIVTHER 001 Phase I/II randomized controlled clinical trial was designed to determine whether the mode of DNA vaccination d...
Most antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs) are thought to act by permeabilizing cell membranes. For antimicrobial therapy, selectivity for pathogens over mammalian cells is a key requirement. Understanding membrane selectivity is thus essential for designing AMPs and SMAMPs to complement classical antibiotics in the futu...
Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loa...
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was inv...
Background:
The frequency of different types of alopecia is not clearly reported in recent studies.
Objective:
To analyze the frequency of the types of alopecia in patients consulting at specialist hair clinics (SHC) and to assess for global variations.
Methods:
Multicenter retrospective study including data from patients evaluated at referral...
Zusammenfassung
Rheumatologische Erkrankungen können sich in einer großen Vielfalt an der Haut manifestieren. Das Spektrum reicht von flüchtigen Exanthemen bis zu tiefer Sklerosierung, Vaskulitis und Pannikulitis. Dank der Zugänglichkeit für Inspektion, Dermatoskopie, Palpation und Biopsien können dermatologische Mitbeurteilungen wertvolle Hinweise...
Based on experimental drug concentration profiles in healthy as well as tape-stripped ex vivo human skin, we model the penetration of the antiinflammatory drug dexamethasone into the skin layers by the one-dimensional generalized diffusion equation. We estimate the position-dependent free-energy and diffusivity profiles by solving the conjugated mi...
Background:
Frontal fibrosing alopecia (FFA) is a cicatricial alopecia mostly affecting the frontotemporal hairline. Its etiology and associated factors remain unclear.
Objective and methods:
An observational, cross-sectional, descriptive study was conducted in France and Germany to identify demographic and health characteristics associated with...
The interactions of nanoparticles with skin and skin cells are complex and depend on the nanoparticle type. The present work provides an overview on the interactions between solid nanoparticles including silica, titanium dioxide, and silver particulates and skin and skin cells on the basis of previous research results. Generally, nanoparticles appl...
The skin surface microbiome and its role in skin diseases have received increasing attention over the past years. Beyond, there is evidence for a continuous exchange with the cutaneous immune system in healthy skin, where hair follicles provide unique anatomical niches. Especially scalp hair follicles form large tubular invaginations, which extend...
Background:
Systems vaccinology allows cutting-edge analysis of innate biomarkers of vaccine efficacy. We have been exploring novel strategies to shape the adaptive immune response, by targeting innate immune cells through novel immunization routes.
Methods:
This randomized phase I/II clinical study (n=60 healthy subjects aged 18-45 years old) u...
The penetration of topically applied tacrolimus formulated in micelles into murine skin is reported, measured by X-ray microscopy. Tacrolimus and micelles are probed for the first time by this high spatial resolution technique by element-selective excitation in the C 1s- and O 1s-regimes. This method allows selective detection of the distribution a...
In reconstructed skin and diffusion cell studies, core-multishell nanocarriers (CMS-NC) showed great potential for drug delivery across the skin barrier. Herein, we investigated penetration, release of dexamethasone (DXM), in excised full-thickness human skin with special focus on hair follicles (HF). Four hours and 16 h after topical application o...
Dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway has a variety of effects on the immune system and stem cell proliferation. Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are inflammatory scalp conditions resulting in permanent alopecia, which are thought to be related to stem cell damage. Here we investig...
Background
Refined encapsulation approaches in dermatotherapy gain increased interest. There is need of reproducible in vitro systems representing disease features to screen drug delivery systems for preclinical assessment. Inflammatory human skin diseases are commonly accompanied by abnormal epidermal differentiation and barrier impairment. Serine...
Zusammenfassung
Primär vernarbende Alopezien (PVA) werden nach der Klassifikation der North American Hair Research Society nach ihrem prominenten entzündlichen Infiltrat in vier Gruppen eingeteilt: PVA mit lymphozytärem, neutrophilem, gemischtzelligem oder unspezifischem Entzündungsmuster. Der Haarausfall kann subklinisch beginnen und langsam forts...