The integration of biological tissues with conducting polymers is crucial for the advancement of bioelectronics. Although the potential toxicity of some conducting-ink components is an acknowledged constraint for in vivo use, a more fundamental limitation is the lack of molecular understanding of how conducting polymers interact with biological barriers. This study addresses some of the limitations by presenting a novel method for direct polymerization of pyrrole on excised skin in vitro and investigates the evolving skin/conducting polymer interface using electrical impedance spectroscopy (EIS), X-ray diffraction, vapor sorption, and complementary analyses. Direct polymerization of pyrrole on skin is performed by applying an aqueous pyrrole solution to the dermal side and an oxidant (ferric ion solution) on the stratum corneum (SC) side of the skin membrane fixed in a Franz cell. EIS measurements show a marked reduction in skin barrier resistance after PPy formation, whereas control experiments produced the opposite trend, confirming that the resistance drop arises specifically from polymerization. Our complementary analyses indicate that polymerization is primarily localized at the solution-SC interface but also support the formation of an electrically coupled pathway across the barrier. These results provide molecular-level insight into polymer-SC interactions, imply the formation of a coherent conductive junction that extends through the SC layers, and inform the design of future skin-integrated bioelectronic materials.

Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch experiments, while EIS characterized pH dependent changes in membrane resistance (Rmem) and effective capacitance (Ceff). Additional analyses assessed microbial conversion of NIA to nicotinic acid during prolonged exposure. Neutral donor pH (7.4) increased NIA permeation by roughly twofold compared with acidic pH (5.0) in both membrane types. Correspondingly, pH 7.4 decreased Rmem and increased Ceff, indicating pH driven changes in SC lipid organization and dielectric behavior. These effects were reversible and likely stem from alterations in SC lipid domains, including pH dependent partial deprotonation of free fatty acids that modifies the continuous lipid regions and introduce localized structural microdefects. Such changes enhance NIA and ion permeability and increase SC dielectric properties at neutral pH. Although microbial conversion of NIA to nicotinic acid was negligible within the first 24 h, it became clearly detectable upon prolonged experiments. In conclusion, donor phase pH is a critical determinant of NIA skin permeation, primarily through reversible modulation of SC lipid structure and transport pathways. These findings highlight the importance of pH control in topical formulations and underscore the need to consider microbiota‑mediated transformations when evaluating the efficacy and safety of skin care products containing NIA.

Niacinamide (NIA) is widely used in skincare for its favorable safety profile, anti-aging effects, and proven clinical efficacy in treating various skin conditions. However, its direct impact on the hydration and molecular organization of the stratum corneum (SC), the primary skin barrier, remains unclear. This study examines how NIA influences the SC's lipid matrix organization, soft keratin structure, and water sorption behavior across varying relative humidity (RH) levels. Using small- and wide-angle X-ray diffraction and dynamic vapor sorption measurements, we compared NIA-treated SC samples to untreated controls under different RHs. The main findings show that while NIA is non-hygroscopic, it enhances water uptake of the SC at high humidity (95% RH). At low humidity (60% RH), NIA swells the keratin monomer spacing, although the SC water content remains low, suggesting a plasticizing effect that could increase SC flexibility in dry conditions. NIA also modifies the diffraction intensities from the lipid matrix differently at 60% and 95% RH, implying that it interacts with the SC lipid matrix and influences the water distribution within the SC lipid and protein domains. These effects appear independent of the investigated dose regime, indicating a specific concentration threshold. Overall, NIA shows distinct interaction with keratin, swelling the spacing between keratin monomers in dry conditions, without acting as a traditional keratolytic agent.

Lipid membranes play a crucial role in regulating the body's water balance by adjusting their properties in response to hydration. The intercellular lipid matrix of the stratum corneum (SC), the outermost skin layer, serves as the body's primary defense against environmental factors. Osmolytes, including urocanic acid (UCA) and glycerol, are key components of the natural moisturizing factor that help the SC resist osmotic stress from dry environments. This study examines the effects of UCA and glycerol (each at 5 mol%) on isolated human SC lipids. For this, different techniques were employed, offering complementary information of the system's multiscale characteristics, including humidity-scanning quartz crystal microbalance with dissipation monitoring, infrared spectroscopy, X-ray diffraction, electrical impedance spectroscopy, and studies of water loss and permeability. Our results show that UCA increases water sorption and makes lipid films more liquid-like at high relative humidity, without significantly altering the lipid lamellar structure, chain order, or orthorhombic chain packing. Lipid films containing UCA exhibited higher water loss, significantly higher model drug permeability, and kinetically faster changes in electrical properties upon contact with aqueous solution compared to control lipids. These observations suggest that UCA reduces lipid cohesion in regions other than the acyl chain-rich leaflets, which may impact SC desquamation. In contrast, glycerol did not influence the hydration or permeability of the SC lipid matrix. However, it increased the proportion of orthorhombic domains at high humidities and slowed the kinetics of the hydration process, as evidenced by slower changes in the dielectric properties of the lipid film. These findings suggest that glycerol enhances lipid cohesion rather than increasing water uptake, which is typically the expected function of humectants. Consequently, UCA and glycerol appear to have distinct roles in maintaining epidermal homeostasis.

The prevailing form of bacterial infection is within the urinary tract, encompassing a wide array of bacteria that harness the urinary metabolome for their growth. Through their metabolic actions, the chemical composition of the growth medium undergoes modifications as the bacteria metabolize urine compounds, leading to the subsequent release of metabolites. These changes can indirectly indicate the existence and proliferation of bacterial organisms. Here, we investigate the use of an electronic tongue, a powerful analytical instrument based on a combination of non-selective chemical sensors with a partial specificity for data gathering combined with principal component analysis, to distinguish between infected and non-infected artificial urine samples. Three prevalent bacteria found in urinary tract infections were investigated, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Furthermore, the electronic tongue analysis was supplemented with 1H NMR spectroscopy and flow cytometry. Bacteria-specific changes in compound consumption allowed for a qualitative differentiation between artificial urine medium and bacterial growth.

Many skin disorders, including cancer, have inflammatory components. The non-invasive detection of related biomarkers could therefore be highly valuable for both diagnosis and follow up on the effect of treatment. This study targets the extraction of tryptophan (Trp) and its metabolite kynurenine (Kyn), two compounds associated with several inflammatory skin disorders. We furthermore hypothesize that lipid-based bicontinuous cubic liquid crystals could be efficient extraction matrices. They comprise a large interfacial area separating interconnected polar and apolar domains, allowing them to accommodate solutes with various properties. We concluded, using the extensively studied GMO-water system as test-platform, that the hydrophilic Kyn and Trp favored the cubic phase over water and revealed a preference for locating at the lipid-water interface. The interfacial area per unit volume of the matrix, as well as the incorporation of ionic molecules at the lipid-water interface, can be used to optimize the extraction of solutes with specific physicochemical characteristics. We also observed that the cubic phases formed at rather extreme water activities (>0.9) and that wearing them resulted in efficient hydration and increased permeability of the skin. Evidently, bicontinuous cubic liquid crystals constitute a promising and versatile platform for non-invasive extraction of biomarkers through skin, as well as for transdermal drug delivery.

Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.).

As a result of the synthesis protocol polyoxyethylene sorbitan monooleate (polysorbate 80, PS80) is a highly complex mixture of compounds. PS80 was therefore separated into its main constituents, e.g. polyoxyethylene isosorbide esters and polyoxyethylene esters, as well as mono- di- and polyesters using preparative high-performance liquid chromatography. In this comprehensive study the individual components and their ethoxylation level were verified by matrix assisted laser desorption/ionization time-of-flight and their thermotropic behavior was analyzed using differential scanning calorimetry and X-ray diffraction. A distinct correlation was found between the average length of the ethylene oxide (EO) chains in the headgroup and the individual compounds' ability to crystallize. Importantly, a critical number of EO units required for crystallization of the headgroup was determined (6 EO units per chain or 24 per molecule). The investigation also revealed that the hydrocarbon tails only crystallize for polyoxyethylene sorbitan esters if saturated. PS80 is synthesized by reacting with approximately 20 mol of EO per mole of sorbitol, however, the number of EO units in the sorbitan ester in commercial PS80 products is higher than the expected 20 (5 EO units per chain). The complex behavior of all tested compounds revealed that if the amount of several of the linear by-products is reduced, the number of EO units in the chains will stay below the critical number and the product will not be able to crystallize by the EO chains.

Sweat is a promising biofluid in allowing for non-invasive sampling. Here, we investigate the use of a voltammetric electronic tongue, combining different metal electrodes, for the purpose of non-invasive sample assessment, specifically focusing on sweat. A wearable electronic tongue is presented by incorporating metal electrodes on a flexible circuit board and used to non-invasively monitor sweat on the body. The data obtained from the measurements were treated by multivariate data processing. Using principal component analysis to analyze the data collected by the wearable electronic tongue enabled differentiation of sweat samples of different chemical composition, and when combined with 1H-NMR sample differentiation could be attributed to changing analyte concentrations.