Imaging mass spectrometry for novel insights into contact allergy - a proof-of-concept study on nickel

Background. In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives. To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method. Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. Results. The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions. This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general

Alkyl Polyglucoside-based delivery systems: In vitro/in vivo skin absorption assessment

Skin permeation and penetration assessment is important not only for determining efficacy of a topical product, but also when comparing different formulations during development. This chapter reviews methods for dermal availability assessment of delivery systems, with their advantages and shortcomings, and examples of their practical application with Alkyl Polyglucoside-based preparations. Alkyl Polyglucosides are used in many different delivery systems with various model actives. Systems stabilized with Alkyl Polyglucoside surfactants provide highly satisfactory cutaneous delivery compared with reference samples. This is mainly attributed to the characteristic APG-based colloidal structure and its ability to provide a combined enhancing effect with co-solvents. Microemulsions for dermal/transdermal delivery are also becoming popular due to their high solubilization potential. Alkyl Polyglucoside surfactants are also being considered for development of nanosystems

Pitfalls in using fluorescence tagging of nanomaterials: Tecto-dendrimers in skin tissue as investigated by cluster-FLIM

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 fluorophore, and nanocarrier may affect the interpretation of these micrographs. False‐negative penetration results due to inter‐ and intramolecular quenching effects are likely. Using tecto‐dendrimers as an example, we present a detailed analysis of pitfalls in the (semi‐)quantitative evaluation of skin nanocarrier penetration. Fluorescence lifetime imaging microscopy (FLIM) allows distinguishing the target fluorescence of dye‐tagged nanocarriers from skin autofluorescence, providing a highly sensitive tool for clear‐cut localization of the nanocarriers. Cluster‐FLIM images reveal that FITC‐labeled tecto‐dendrimers penetrate the stratum corneum of human skin ex vivo and reconstructed human skin but do not cross the tight junction barrier.Fil: Volz, Pierre. Freie Universitat Berlin; AlemaniaFil: Schilrreff, Priscila. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brodwolf, Robert. Freie Universitat Berlin; AlemaniaFil: Wolff, Christopher. Freie Universitat Berlin; AlemaniaFil: Stellmacher, Johannes. Freie Universitat Berlin; AlemaniaFil: Balke, Jens. Freie Universitat Berlin; AlemaniaFil: Morilla, María José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zoschke, Christian. Freie Universitat Berlin; AlemaniaFil: Schäfer-Korting, Monika. Freie Universitat Berlin; AlemaniaFil: Alexiev, Ulrike. Freie Universitat Berlin; Alemani