Photodynamic therapy (PDT) of skin cancer relies on the generation of reactive oxygen species (ROS), but experimental systems that accurately model photodynamic reactions are limited. The aim of the present in vitro study was therefore to develop and validate a model system enabling mechanistic investigation under controlled conditions. We combined a split-thickness skin membrane with a monoolein-derived bicontinuous cubic liquid crystalline phase containing the endogenous photosensitiser protoporphyrin IX (PpIX) to form a tissue model. Light irradiation was used to activate the PpIX, and the resulting decrease in oxygen concentration, associated with ROS formation, was monitored in real time using a Clark electrode. Electron spin resonance was employed for singlet oxygen detection. Incorporation of PpIX did not affect the structural properties of the cubic phase within the tested concentration span. Spectroscopic measurements indicated that PpIX dissolves in the lipid matrix, although optical microscopy revealed particle aggregation at concentrations above 400 μg/g. Fluorescence microscopy demonstrated a concentration-dependent increase in signal up to 400 μg/g, followed by a plateau consistent with aggregation. Real-time monitoring of oxygen depletion, expressed as the total decrease in oxygen concentration during irradiation, showed a concentration-dependent increase up to 3 μg/g PpIX, beyond which a plateau was observed. In contrast, kinetic analysis demonstrated increasing oxygen consumption rates up to 400 μg/g. The inclusion of a split-thickness skin membrane maintained oxygen depletion associated with ROS formation and allowed reliable monitoring of the photodynamic response under the investigated conditions. Electron spin resonance provided independent evidence that the PpIX concentration-dependent oxygen depletion observed during irradiation was associated with increased singlet oxygen formation. In conclusion, the proposed system provides a stable in vitro platform for studying photodynamic reactions and the influence of photosensitiser concentration under controlled conditions, offering mechanistic insight into PDT-related processes.

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.

Iodine is a well-established antimicrobial agent, but its clinical use is limited by low chemical stability and adverse effects. This work investigates iodine loading into degradable starch microspheres (DSM), elucidating iodine–starch interactions, and structural changes after iodine uptake. Iodine complexation was achieved using a KI/I₂ system, yielding a characteristic purplish-red coloration within the DSM. Swelling and sedimentation analyses showed a slight reduction in DSM density after iodine absorption, without negative impact on hydration capacity. A UV–Vis spectrophotometric method targeting the triiodide band at 352 nm enabled robust quantification of iodine by leveraging equilibrium among iodine species. Sorption isotherms revealed cooperative binding behavior, with iodine uptake increasing nonlinearly in response to the external iodine concentration. Small- and wide-angle X-ray scattering (SWAXS) showed iodine-induced ordering across multiple length scales, including a reduction in the dynamic correlation length and the emergence of characteristic peaks associated with iodine–amylose complex. These results elucidate the physicochemical mechanisms governing iodine incorporation into DSM and highlight the structural consequences of loading, providing a framework for designing starch-based carriers for controlled iodine release.

BACKGROUND: Staphylococcus aureus and Staphylococcus epidermidis normally coexist on the skin of healthy individuals. Their ratio and pathogenicity, however, change with different skin diseases and thus, the ability to control bacterial growth on the skin is important. Propylene glycol (PG), a widely used component in topical formulations, has been proved to have antimicrobial activity.

OBJECTIVES: To investigate the concentration-dependent antimicrobial properties of PG against S. aureus and S. epidermidis skin isolates in mono- and co-culture at neutral (pH 7.4) and mildly acidic (pH 5) conditions.

RESULTS AND DISCUSSION: The minimum inhibitory concentration of PG was 12.5% at both pH 5 and pH 7.4 for the selected bacterial strains. The viability of S. aureus exposed to 12.5% PG was lower at pH 5 than at pH 7.4, and post-treatment regrowth of S. aureus occurred slowly at acidic pH. When both bacterial strains were incubated in media containing 12.5% PG at pH 5 for 48 hours, S. epidermidis retained significantly higher viability, while at pH 7.4, the results were opposite.

CONCLUSIONS: Under the acidic conditions of healthy skin, pathogenic S. aureus is more suppressed by 12.5% PG than commensal S. epidermidis.

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.

Purpose: To evade immunosurveillance many cancers convert tryptophan (Trp) into kynurenine (Kyn), which induces immunotolerance and suppresses immune responses. Elevated Kyn amounts have been found in blood from patients with cutaneous melanoma. This study aimed to investigate whether higher Kyn abundance and lower Trp abundance can be detected on the surface of cutaneous melanoma lesions compared with adjacent non-lesional skin.

Methods: Sixteen patients with suspected melanomas were enrolled in this study. All lesions were excised and histopathologically diagnosed: 7 lesions were diagnosed as invasive malignant melanomas (MM), 6 as melanomas in situ (MIS), and 3 as benign lesions (BL). Non-invasive metabolite sampling was performed by tape stripping of suspected skin lesions and adjacent healthy non-lesional (NL) skin. Trp, Kyn, tyrosine (Tyr), and phenylalanine (Phe) were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Electrical impedance spectroscopy (EIS) measurements were conducted to assess skin barrier integrity.

Results: Levels of all metabolites, Tyr (x6), Phe (x6), Trp (x5), and Kyn (x3), were significantly higher in MM lesions compared with adjacent NL skin, resulting in an elevated Trp/Kyn ratio. Trp levels increased less than Phe and Tyr levels, suggesting a potential increase in Trp depletion. Skin resistance in MM lesions was half that of NL skin. No differences were observed between MIS or BL and NL skin.

Conclusions: Non-invasive skin sampling revealed elevated Tyr, Phe, Trp and Kyn levels in MM skin, which is likely the result of compromised skin barrier at this stage of cutaneous melanoma.

Introduction: To minimize the risk of developing foot-ulcers, persons with diabetes are given the advice to daily inspect their feet and to apply skincare formulations. However, commercially available skincare products have rarely been developed and evaluated for diabetes foot care specifically. The primary aim of this randomized controlled trial (RCT) is to evaluate the effects in reducing foot xerosis in persons with diabetes without footulcers using two skincare creams containing different humectants (interventions) against a cream base nonhumectant (comparator). Secondary outcomes are to evaluate differences on skin barrier integrity, lowmolecular weight biomarkers and skin microbiota, microcirculation including transcutaneous oxygen pressure, degree of neuropathy, and HbA1c between intervention-comparator creams. Methods: Two-armed double-blind RCT, registered in ClinicalTrials.gov Identifier: NCT06427889. With 80 % power, two-tailed significance of 2.5 % in each arm, 39 study persons is needed in each arm, total 78 persons, 98 including dropouts, to be able to prove a reduction of at least one category in the Xerosis Severity Scale with the intervention creams compared to the comparator. In one arm, each participant will treat one foot with one of the intervention creams (Oviderm (R) or Canoderm (R)), while the opposite foot will be treated with the comparator cream (Decubal (R) lipid cream), twice a day. If needed, participants are enrolled after a wash-out period of two weeks. The participants will undergo examinations at baseline, day 14 and day 28. Discussion: This RCT evaluate the potential effects of humectants in skin creams against foot xerosis in persons with diabetes.

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.

The aim of this study was to investigate the effect of various skin preservation protocols on in vitro drug permeation, epidermal-dermal drug distribution, and electrical impedance properties of skin membranes. Acyclovir (AC) and methyl salicylate (MS) were selected as model drugs due to their different physicochemical properties and skin metabolic profiles. In particular, AC is relatively hydrophilic (logP -1.8) and not expected to be affected by skin metabolism, while MS is relatively lipophilic (logP 2.5) and susceptible to metabolism, being a substrate for esterase residing in skin. Skin from pig ears was used and freshly excised into split-thickness membranes, which were divided and immediately stored at five different storage conditions: a) 4 °C overnight (fresh control), b) 4 °C for 4 days, c) and d) -20 °C for 6 weeks and one year, respectively, and e) -80 °C for 6 weeks. Based on the combined results, general trends are observed showing that fresh skin is associated with lower permeation of both model drugs and higher skin membrane electrical resistance, as compared to the other storage conditions. Interestingly, in the case of fresh skin, significantly lower amounts of MS are detected in the epidermis and dermis compartments, implying higher levels of ester hydrolysis of MS (i.e., higher esterase activity). In line with this, the concentration of salicylic acid (SA) extracted from the dermis is significantly higher for fresh skin, as compared to the other storage conditions. Nevertheless, for all storage conditions, substantial amounts of SA are detected in the receptor medium, as well as in the epidermis and dermis, implying that esterase activity is maintained to some extent in all cases. For AC, which is not expected to be affected by skin metabolism, freeze storage (protocols c-e) is observed to result in higher accumulation of AC in the epidermis, as compared to the case of fresh skin, while the AC concentration in dermis is unaffected. These observations can be rationalized primarily by the observed lower permeability of fresh skin towards this hydrophilic substance. Finally, a strong correlation between AC permeation and electrical skin resistance is shown for individual skin membranes irrespective of storage condition, while the corresponding correlation for MS is inferior. On the other hand, a strong correlation is shown for individual membranes between MS permeation and electrical skin capacitance, while a similar correlation for AC is lower. The observed correlations between drug permeability and electrical impedance open up for standardizing in vitro data for improved analysis and comparisons between permeability results obtained with skin stored at different conditions.