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In silico techniques, such as physiologically based pharmacokinetic modeling (PBKP), are recently gaining importance. Computational methods in drug discovery and development and the generic drugs industry enhance research effectiveness by saving time and money and avoiding ethical issues. One key advantage is the ability to conduct toxicology studies without risking harm to living beings. This study aimed to repurpose the multi‐phase multi‐layer mechanistic dermal absorption (MPML MechDermA) PBPK model for simulation permeation through porcine ear skin under in vitro conditions. The work was divided into four steps: (1) the development of a pig ear skin model based on a previously collected dataset; (2) testing the model's ability to discriminate permeation between pig ear, human abdomen, and human back skin; (3) development of a caffeine permeation model; and (4) testing the caffeine model's performance against in vitro generated data sourced from the scientific literature. Data from 31 manuscripts were used for the development of the pig skin model. Based on these data, values specific to pig skin were found for 22 parameters of the MPML MechDermA model. The model was able to discriminate permeation between pig and human skin. A caffeine model was developed and used to simulate seven experiments identified in the literature. The model's performance was assessed by comparing simulated to observed results. Based on a visual check, all simulations were considered acceptable, whereas three out of seven experiments met the twofold difference criterion. The variability of the experimental data was considered the biggest challenge for reliable model assessment. In silico techniques, like physiologically based pharmacokinetic modeling, enhance drug research effectiveness by saving time and money and reducing ethical concerns. In this study, the multi‐phase multi‐layer mechanistic dermal absorption model was repurposed for simulating permeation through porcine ear skin under in vitro conditions. The porcine ear skin model was developed, and it was able to discriminate permeation between pig and human skin. Afterward, it was used to build caffeine permeation model. The model was tested against experimental data sourced from scientific literature. [ABSTRACT FROM AUTHOR]

Introduction and Purpose: Microplastics, ubiquitous environmental contaminants, are increasingly recognized for their potential to impact human health. This review aims to consolidate existing knowledge on the pathways through which microplastics interact with biological systems and to elucidate their health implications. State of Knowledge: Microplastics are pervasive in various environments, from aquatic to terrestrial ecosystems, and they eventually enter the human body via ingestion, inhalation, or dermal absorption. Studies have suggested that microplastics carry toxic substances, such as heavy metals and organic pollutants, which are known endocrine disruptors and carcinogens. Additionally, the physical presence of microplastics has been linked to inflammation and other negative health outcomes. Research in this field is complex and interdisciplinary, involving toxicology, environmental science, and public health disciplines. Summary: The presence of microplastics in the human body is concerning, and there is a clear need for further research to understand the extent of health risks associated with chronic exposure. Public health strategies should include both reducing microplastic pollution and strengthening regulations on plastic waste. Meanwhile, medical professionals should consider the potential for microplastic exposure when diagnosing and treating chronic conditions. Future research should aim to clarify the mechanisms of toxicity and establish safe levels of exposure, with a multidisciplinary approach being essential for comprehensive understanding and effective intervention. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods Results Conclusion To compare and evaluate the differences between EGCG and phosphatidylcholine‐encapsulated EGCG in terms of their anti‐inflammatory and antioxidant capacities.In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine‐encapsulated EGCG. Subsequently, the disparity in anti‐inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine‐encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions.The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine‐encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine‐encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity.The percutaneous absorption and anti‐inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine‐encapsulated EGCG in cosmetic applications, specifically for fostering products with anti‐inflammatory and antioxidant benefits. [ABSTRACT FROM AUTHOR]

Background: Berberine, a phytochemical, possesses remarkable potential for multitargeted drug therapy in microbial infections, wound healing and anti-inflammatory applications. However, its clinical utility in skin and other diseases is constrained due to its high aqueous solubility and inadequate dermal and intestinal absorption, resulting in low absolute bioavailability. Objectives: The current investigation endeavors to develop a microemulsion loaded with berberine to enhance its solubility and therapeutic effects specifically for skin diseases, while comparing its efficacy with a simple emulsion. Materials and Methods: In this study, an optimized oil-in- water (o/w) type of emulsion and microemulsion were formulated utilizing berberine isolated from Berberis aristata roots, along with soy lecithin, oleic acid, Tween 80, and ethanol. The microemulsion and emulsion were subjected to characterization employing parameters such as FTIR, particle size, zeta potential, transmittance, viscosity, and stability. The formulations were assessed for their therapeutic effects through in vitro antioxidant, anti-inflammatory, and anti, microbial assays, encompassing six strains of micro, organisms comprising bacteria and fungi. Results: The investigation successfully generated a thermodynamically stable o/w type of microemulsion, which exhibited improved transparency and formed a clear solution. Characterization results, including particle size, zeta potential, viscosity, and conductivity measurements, fell within the acceptable range. The therapeutic evaluation demonstrated a substantial enhancement in the in vitro antioxidant, anti-inflammatory, and anti, microbial activity of berberine microemulsion compared to the plain berberine solution. Conclusion: This study concludes that berberine can be effectively incorporated into a microemulsion system. When topically applied, the microemulsion form exhibits significantly higher therapeutic efficacy against skin diseases compared to the conventional emulsion of berberine. [ABSTRACT FROM AUTHOR]

Introduction: Ceramides are essential epidermal constituents that play a critical role in skin moisturization treatment as a raw material in cosmetics formulation. Recently, ceramides have been known to be frequently applied in various cosmetic formulations. Despite ceramide's beneficial characteristics, academic research regarding ceramides and their skin absorption remains insufficient. Therefore, our study conducted clinical research employing Raman spectroscopy to investigate the effects of ceramides on skin absorption to enhance the understanding of ceramides' dermatological functionality and their topical application in cosmetics science. Materials and Methods: Twenty healthy individuals with dry skin have participated in this clinical trial. In this double‐arm designed trial, the test group received an investigational product with ceramides (5000 ppm) and a control group received an investigational product without the ceramides while all other components remained identical. The subjects visited the clinical research center and acclimatized for 30 min in constant humidity and temperature for equilibrium, subsequently conducting a measurement. Before the trial, the research subject's target site (lower arm area) was kept clean, devoid of any cosmetic administering 24 h before the trial when investigational product was topically applied. Results: Our findings with Raman spectroscopy statistically demonstrate that skin absorption amount, speed and depth for both groups improved overall (p < 0.05) after administration of the investigational product. Notably, the test group received an investigational product with ceramides (5000 ppm) indicating superior effectiveness across all parameters compared to a control group from comparison analysis of each parameter (p < 0.05). Conclusion: This study concludes that ceramide‐containing cosmetics provide a beneficial effect on skin absorption via visual and statistical results of Raman spectroscopy analysis. [ABSTRACT FROM AUTHOR]

Alternative plasticizers such as diisononyl-1,2-cyclohexanedicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), and di(2-ethylhexyl) adipate (DEHA) are progressively replacing phthalates in many consumer and professional products because of adverse effects on reproduction associated with some phthalates. Human exposures to these phthalate substitutes can occur through ingestion, skin absorption and inhalation. Skin uptake can lead to greater concentration at the target organs compared to ingestion because the skin exposure route bypasses the first-pass effect. Skin absorption studies are almost absent for these alternative plasticizers. We therefore wanted first, to characterize skin absorption of a mixture containing DINCH, DEHA and DEHTP in vitro using a flow-through diffusion cell system with ex vivo human skin, quantifying their respective monoester metabolites (mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH), mono-2-ethylhexyl adipate (MEHA), mono-2-ethylhexyl terephthalate (MEHTP), respectively); second, to validate these results by exposing five human volunteers to this mixture on their forearm and quantifying the corresponding urinary metabolites (including the monoesters and their oxidation products). Our study showed that two of these alternative plasticizers, DEHTP and DINCH, did not permeate skin showing as quantifiable metabolite levels in vitro and only traces of DEHA were quantified as its monoester metabolite, MEHA. Permeation coefficient (Kp) 0.06 and 55.8*10−7 cm/h for neat and emulsified DEHA, respectively, while the permeation rate (J) remained low for both (0.005 and 0.001 µg/cm2/h, respectively). Participants exposed to a mixture of these three plasticizers did not have noteworthy urinary concentrations of their respective metabolites after 24 hours post-application. However, the alternative plasticizer mixture was completely absorbed after six hours post-application on the forearms of the human volunteers, and the urinary elimination curves showed a slight increase after 24 hours post-application. Further studies on skin absorption of these substances should follow the urinary elimination kinetics of these metabolites more than 24 hours post-application. We also recommend quantifying the parent compounds in the in vitro diffusion experiments. [Display omitted] • Urinary excretion of DINCH monoester was slow in skin-exposed participants. • DEHTP and DEHA monoesters were not detected in urine from participants. • DEHA permeated skin in vitro as its monoester. • DEHTP and DINCH did not permeate skin in vitro as their monoesters. [ABSTRACT FROM AUTHOR]

2-Ethylhexyl salicylate (EHS) is an organic UV filter which is used in sunscreen and other personal care products. The dermal uptake of EHS was studied in several dermal-exposure experiments. This paper aims to coherently assess urine samples after dermal exposure for the biomarkers EHS, 5OH-EHS, 5oxo-EHS, and 5cx-EPS as well as further biomarkers of interest, specifically 4OH-EHS, 4oxo-EHS, 2OH-EHS, and 6OH-EHS, for the first time. Samples from 18 participants of a pre-existing dermal exposure study under real-life conditions were reassessed using a comprehensive LC-MS/MS method. EHS accounts for 34 % of the cumulative excretion of all analytes within 24 h after exposure, followed by 5OH-EHS (19 %), 5cx-EPS (18 %), 4OH-EHS (15 %) and 5oxo-EHS (11 %). Further metabolites were only quantified in minor amounts. EHS as the most prominent excretion parameter in this study demonstrates the missing first-pass effect after dermal absorption. Furthermore, the applied novel comprehensive analytical procedure revealed oxidation at the ω (5cx-EPS, 6OH-EHS), ω-1 (5OH-EHS, 5oxo-EHS), and ω-2 positions (4OH-EHS, 4oxo-EHS) in the main chain of the ethylhexyl group as well as oxidation in the side chain (2OH-EHS). The presented data are of high relevance for a reliable toxicological risk assessment of dermal exposure to EHS. [Display omitted] • Toxicokinetic assessment of 2-ethylhexy salicylate (EHS) and metabolites. • Real-life dermal exposure scenario. • Confirming EHS, 5OH-EHS, 5oxo-EHS and 5cx-EPS as relevant biomarkers. • Showing relevant oxidation at ω, ω-1, ω-2 position in the ethylhexyl chain. • Formation of considerable amounts of 4OH-EHS after dermal exposure to EHS. [ABSTRACT FROM AUTHOR]

Significance: As an inflammatory and autoimmune skin condition, psoriasis affects 2–3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis. Objective: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption Methods: The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis. Results: Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis. Conclusion: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis. [ABSTRACT FROM AUTHOR]

Firefighter occupational exposures were categorized as a class 1 (known) carcinogen by the International Agency for Research on Cancer in 2022. As a result, firefighters have become heavily focused on identifying effective and easy to implement decontamination strategies to reduce their chemical exposures. Skin decontamination using wipes post-exposure is one decontamination strategy that every firefighter has available to them. However, firefighters have expressed concerns over the ingredients in the wipe solution increasing dermal absorption. The goal of this study was to determine if the ingredients in skin decontamination wipe solution had any enhancement effect on the dermal absorption of phenanthrene. To determine any enhancement effects, the additive solution of four skin decontamination wipe products was applied to porcine skin 15 min after chemical dosing. The absorption of phenanthrene was tested in vitro using a flow-through diffusion cell system over eight hours. The wipe solution effects on dermal absorption were determined by measuring multiple absorption characteristics including cumulative absorption (µg/cm2), absorption efficiency (% dose absorbed), lag time (minutes), flux (µg/cm2/h), diffusivity (cm2/h), and permeability (cm/h). No penetration enhancement effects were observed in any of the skin decontamination wipe solutions tested; rather, all wipe solutions decreased the absorption of phenanthrene. Slight differences in cumulative absorption among two pairings of skin decontamination wipe solutions, wipes 1 and 3 vs. wipes 2 and 4, were observed, indicating that some ingredients may impact dermal absorption. These findings show that firefighters should continue using skin decontamination wipes to reduce their dermal exposures to fireground contaminants with little concern of increasing the absorption of phenanthrene. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are found in a variety of places including cosmetics, rain jackets, dust, and water. PFAS have also been applied to occupational gear to protect against water and oils. However, PFAS have been identified as immunosuppressants and perfluorooctanoic acid (PFOA), a specific PFAS, has been identified as carcinogenic. Since there is a risk for dermal exposure to these compounds, there is a need to characterize their dermal absorption. Using in vitro flow-through diffusion, skin permeabilities were determined for 14C-labeled perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA), and perfluorobutanoic acid (PFBA) using porcine skin. Tests were conducted over 8 h with either acetone or artificial perspirant as the vehicle. PFBA was found to have greater permeability than PFHxA, likely due to having a smaller molecular weight. The dosing vehicle did not appear to impact permeability rates but impacted the disposition through the skin model. While these PFAS compounds showed a low permeability rate through the skin membranes, they can stay in the skin, acting as a reservoir. [ABSTRACT FROM AUTHOR]

Hair relaxers have been suggested as a source of exposure to parabens and phthalates. However, dermally absorbed doses of these chemicals resulting from consumer use of hair relaxers have yet to be quantified, and results from epidemiological studies have consistently demonstrated that there is no increased risk for hormone-sensitive, reproductive cancers associated with use of hair relaxers among Black women. Therefore, dermal absorption of parabens and phthalates associated with hair relaxer use for several commercially available hair relaxer kits was modeled using IH SkinPerm™. The chemicals detected in the hair relaxer kits included methylparaben (MP), ethylparaben (EP), butylparaben (BP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and the phthalate substitute bis(2-ethylhexyl) adipate (DEHA). The daily absorbed dose ranges (mg/kg/day), standardized over a year of product use, were as follows: 8.64 × 10−5-0.00116 MP, 2.30 × 10−8-3.07 × 10−6 EP, 3.24 × 10−8-4.33 × 10−6 BP, 8.65 × 10−9-1.15 × 10−6 DEP, and 8.94 × 10−7-0.000119 DEHP for Kit #1; 8.44 × 10−5-0.00113 MP and 7.91 × 10−5-0.00106 DEP for Kit #2; and 2.49 × 10−6-3.33 × 10−5 MP, 1.52 × 10−8-2.03 × 10−6 EP, 3.29 × 10−9-4.39 × 10−7 DEP, and 3.11 × 10−6-4.14 × 10−5 DEHA for Kit #3. These absorbed doses were well below applicable health-based guidance values, indicating consumer exposure from product use is not expected to pose a health risk. These results provide valuable information for health risk evaluations for hair relaxer use. [ABSTRACT FROM AUTHOR]

Woman's breast cancer has always been among the top ten causes of cancer death, and nearly 2% to 5% of locally advanced breast cancers develop a fungating breast wound. Fungal breast cancer leads to skin ulcers, wound ruptures, and other bacterial infections in patients. Ursolic acid (UA), a natural pentacyclic triterpene compound, is widely distributed in many fruits. Previous studies demonstrated that UA has anti-breast cancer, antifungal, and improved wound-healing effects. UA, however, had poor water solubility and low bioavailability, restricting its clinical application. Nanofibers have the advantages of rapid dissolution, improved stability, and bioavailability of active ingredients. We had successfully prepared ursolic acid nanofibers (UANFs) and effectively improved their water solubility and skin penetration. UANFs can increase water solubility by improving the physicochemical properties, including increased surface area, intermolecular bonding with excipients, and amorphous transformation. Furthermore, UANFs had better anti-breast cancer activity than raw UA. UANFs inhibited the expression of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho-extracellular regulated protein kinases (ERK)1/2, and induced cleaved caspase-3 protein expression, but had no effect on the raw UA treatment. In summary, UANFs enhanced the skin absorption of UA and improved its anti-breast cancer efficacy. We expect that UANFs can be used as an anti-breast cancer treatment and reduce the discomfort of breast cancer patients during dressing changes, but more detailed efficacy and safety trials still need to be conducted in further studies. [ABSTRACT FROM AUTHOR]

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies. [ABSTRACT FROM AUTHOR]

The aim of the dermal acute toxicity test is to identify the intrinsic toxicity of a product by assessing its hazard potential following acute skin exposure. This test also provides preliminary data that can be used to determine the appropriate dosage level and guide the design of subsequent toxicity studies, including determining the LD50 value and information about skin absorption. In this study, female rats (Rattus Nervegicus) are used as test subjects. The test material is prepared by diluting 15 ml of the sample to a final concentration of 994.9 mg/mL. The rats are exposed to the material for 24 hours. Post-exposure, microanatomical observations, and surgery in the abdominal and thoracic areas revealed no abnormalities. [ABSTRACT FROM AUTHOR]

This study quantified the concentrations of trace and heavy elements, including Al, K, Ca, Mg, Zr, Ti, La, Ce, Mn, Cr, Zn, and Nd, in soil samples from Tukwikwi. It also assesses the potential human health risks posed by exposure to these metals through ingestion, inhalation, and dermal absorption for both children and adults. The study area lies in Hadejia flood plain between latitudes 12°10′ N to 13°0′ N and longitudes 10°15′ E to 11°30′ E. The result showed that the mean concentrations of Al (47,140 mg/kg), K (23,110 mg/kg), Fe (18,020 mg/kg), Mg (7810 mg/kg), Zr (404 mg/kg), and La (64 mg/kg) exceeded the crustal values of Al (25,000 mg/kg), K (10,700 mg/kg), Fe (9800 mg/kg), Mg (7000 mg/kg), Zr (220 mg/kg), and La (30 mg/kg). By contrast, the concentrations of Ca, Cr, Ce, Mn, Ti, Zn, and Nd were lower than the crustal values. These crustal values were used, as there were no regional values that could be used for comparison. The result of the noncarcinogenic health risk assessment showed that Al exhibited the highest value ranging from 5.52×10−1$5.52 \times {{10}^{ - 1}}$ to 7.51×10−1$7.51 \times {{10}^{ - 1}}$ for children and 7.3×10−1$7.3 \times {{10}^{ - 1}}$ to 9.9×10−1$9.9 \times {{10}^{ - 1}}$ for adults. The results also revealed that adults have a higher potential risk than children. The results for the carcinogenic risk (CR) showed that the total CR (TCR) values for Cr ranged from 0 to 3.20×10−4$3.20 \times {{10}^{ - 4}}$ for children and 0 to 4.29×10−4$4.29 \times {{10}^{ - 4}}$ for adults, which are higher than the acceptable limit of 1×10−4$1 \times {{10}^{ - 4}}$. These suggest that there are health concerns for adults and children in the research area. This necessitates the need for monitoring the soil in the study area to reduce potential environmental issues. [ABSTRACT FROM AUTHOR]

Background: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment. Results: We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats. Conclusion: The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens. [ABSTRACT FROM AUTHOR]

The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLi+Gen). We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg. The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium. Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies. The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption. • TMPRSS15 is a novel regulator of lithium response in patients with bipolar disorder. • It is the most likely effector gene at a known lithium response locus. • The gene encodes enterokinase (ENTK), a key modulator of intestinal absorption. • ENTK likely impacts lithium response through the modulation of lithium absorption. [ABSTRACT FROM AUTHOR]

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata. Reversal of alopecia areata with topical TFB NPs treatment by blocking the JAK-STAT signaling pathways, reduced the expression levels of IFN-γ and the frequencies of NKG2D+CD8+ T cells, restored immune environment and promoted hair regrowth. [Display omitted] • Ex vivo mouse hair follicles model was used to assess formulations. • Hair follicles blocked skin model was used to evaluate drug permeation. • Cationic nanostructured carriers minimize systemic circulation and maximize hair follicle targeting. • The formulation restored immune privilege and ensured safe topical delivery for the treatment of alopecia areata. [ABSTRACT FROM AUTHOR]

The objective of this research was to compare the functional differences between azelaic acid and chitosan-coated azelaic acid as cosmetic raw materials in terms of skin absorption efficiency, exfoliation, anti - inflammatory and 5α-reductase inhibition. The results showed that the skin absorption of azelaic acid was significantly higher compared to azelaic-chitosan. In terms of exfoliation, both azelaic acid and azelaic-chitosan had a certain exfoliating efficacy. However, compared to azelaic-chitosan, azelaic acid alone resulted in a 25.86% higher number of detached corneocytes and a 27.80% higher total protein content. In terms of anti-inflammation, azelaicchitosan at the same concentration showed significantly greater inhibitory effects on inflammatory factors such as tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) compared to decanoic acid. Besides, there was no significant difference in inhibitory activity of 5α-reductase between the two groups. These results suggested that both materials had their advantages in terms of their efficacy as cosmetic ingredients. This study contributed to harnessing the potential benefits of azelaic acid and chitosan coating as cosmetic ingredients while providing valuable reference data for evaluating the application potential of chitosan as a coating material in cosmetics. [ABSTRACT FROM AUTHOR]

Firefighters face significant risks of exposure to toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), during fire suppression activities. PAHs have been found in the air, on the gear and equipment, and in biological samples such as the skin, breath, urine, and blood of firefighters after fire response. However, the extent to which exposure occurs via inhalation, dermal absorption, or ingestion is unclear. In this study, three PAHs, naphthalene, phenanthrene, and benzo[a]pyrene, were applied to porcine skin in vitro in an artificial sweat solution to better gauge firefighters' dermal exposures while mimicking their sweaty skin conditions using an artificial sweat dosing vehicle. Multiple absorption characteristics were calculated, including cumulative absorption, percent dose absorbed, diffusivity, flux, lag time, and permeability. The absorption of the PAHs was greatly influenced by their molecular weight and solubility in the artificial sweat solution. Naphthalene had the greatest dose absorption efficiency (35.0 ± 4.6% dose), followed by phenanthrene (6.8 ± 3.2% dose), and lastly, benzo[a]pyrene, which had the lowest absorption (0.03 ± 0.04% dose). The lag times followed a similar trend. All chemicals had a lag time of approximately 60 min or longer, suggesting that chemical concentrations on the skin may be reduced by immediate skin cleansing practices after fire exposure. [ABSTRACT FROM AUTHOR]

Background Aims Patients/Methods Results Conclusions Recent advancements in dermatological therapeutics have highlighted the need for treatments that enhance skin regeneration and healing. Diamond‐Augmented Zinc Oxide (ND‐ZnO) technology combines zinc oxide with diamond particles in a unique core‐shell structure, offering a multifaceted approach to overall skin health.This study evaluates the efficacy of ND‐ZnO in promoting human dermal fibroblast migration and growth, enhancing total collagen synthesis, and improving transdermal delivery of active ingredients as a daily comprehensive skin regeneration topical therapy.In vitro assays assessed wound healing, collagen production, and skin absorption. Human Dermal Fibroblasts (HDFs) were used in scratch wound assays. Collagen synthesis was quantified using enzyme‐linked immunosorbent assays (ELISA). Permeation tests were performed on reconstructed human epidermal tissues to evaluate niacinamide absorption. Clinical case studies validated ND‐ZnO efficacy in post‐CO₂ laser treatments and Actinic Keratosis removal recovery.ND‐ZnO increased HDF migration by 198% compared to controls. Collagen synthesis assays showed a 71.3% restoration of collagen production in aged HDFs. Skin permeation studies revealed a 203% increase in niacinamide skin absorption with ND‐ZnO. Clinical case studies demonstrated faster and more effective healing post‐ablative CO₂ laser and significant improvements in Actinic Keratosis recovery.ND‐ZnO technology enhances wound healing, collagen synthesis, and active ingredient delivery, offering substantial benefits for daily skin regeneration and other dermatological applications. This innovative approach holds promise for advancing dermatological therapeutics, providing comprehensive skin care solutions that address both protective and regenerative needs. [ABSTRACT FROM AUTHOR]

Whether from environmental and occupational hazards or from topical pharmaceuticals, the human skin comes into contact with various chemicals every day. In vivo experiments not only require large investments of both time and money, but in vivo experiments can also be unethical due to the need to intentionally or incidentally expose humans or animals to toxic chemicals. Comparatively, in vitro experiments offer ethical and financial advantages when combined with the opportunity to selectively choose chemicals for experimentation. With in vivo experimentation being so infeasible, many scientists have chosen to make their in vitro data available publicly. Using these data, a detailed database containing 73 chemicals was created with a robust set of descriptors to be used in connection with mathematical modeling to predict diffusion, permeability, and partition coefficients. This resulting database is tailored to be easily used in various coding languages. [ABSTRACT FROM AUTHOR]

Background: Cetirizine is a second-generation antihistamine with anti-allergy and anti-itching properties. The topical formulation of this medicine is used in androgenic alopecia treatment. Due to the hydrophilic nature of cetirizine, its skin absorption is negligible, so to increase its absorption, various enhancers were examined to see which can be used in the design of a topical formulation. Methods: First, the skin was exposed to enhancers, including eucalyptus, menthol, Tween 80, propylene glycol, and oleic acid, for 1 or 2 hours. Then, the permeability parameters of the cetirizine solution and the structural changes of the skin after exposure to enhancers were analyzed by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) techniques. Results: The obtained results show that all used enhancers increased the permeability of the drug cetirizine compared to water. Various mechanisms, such as liquefaction of lipids, destruction of lipid structure, and irreversible denaturation of intracellular keratin, are involved in the increase in drug penetration caused by eucalyptus, mint, Tween 80, propylene glycol, and oleic acid. Conclusions: The results showed that among the studied absorption enhancers, eucalyptus and Tween 80 had the strongest, and propylene glycol had the weakest absorption enhancement effect after 2- and 1-hour pre-contact, respectively. [ABSTRACT FROM AUTHOR]

Introduction and aim. Orthopedic surgeries often require acquiring cancellous bone grafts, commonly sourced from the iliac crest. Traditional harvesting methods pose risks of donor site morbidity, prompting interest in minimally invasive techniques. This study introduces and evaluates the efficacy and safety of a percutaneous technique using a tap and drill sleeve for iliac crest bone graft harvesting. This study aims to assess outcomes and complications associated with a minimally invasive percutaneous technique for iliac crest bone graft harvesting through a retrospective analysis of twenty patients undergoing upper limb reconstructive surgery. Material and methods. A retrospective analysis was conducted on twenty patients who underwent upper limb reconstructive surgery between January and March 2023. The technique involved making a bone deep stab incision, precisely positioning a drill and tap sleeve, utilizing controlled tapping techniques, and extracting the graft. Post-operative assessments included evaluating pain levels, ambulation, and patient satisfaction. Results. The minimally invasive percutaneous technique demonstrated favorable outcomes, with reduced donor site morbidity observed. Within 24 hours post-operatively, 70% of patients reported low visual analogue scale scores, and 80% regained normal walking ability. No instances of post-operative paresthesia were reported. Conclusion. The examined minimally invasive percutaneous technique for iliac crest bone graft harvesting showed reliability and safety, particularly in low resource settings. Utilizing basic orthopedic tools such as tap and drill sleeves offers accessibility and affordability. This approach could effectively mitigate donor site morbidity in orthopedic reconstructive treatments. [ABSTRACT FROM AUTHOR]

AbstractA hydrogel formulation containing arbutin was developed for use as a topical cosmetic product aimed at enhancing the anti-melanogenesis effect and skin delivery. To develop Arbutin-hydrogel, 1% arbutin was incorporated into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the arbutin-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, toxicity study and, skin absorption test were employed to assess the arbutin-hydrogel. The swelling percentages of arbutin-hydrogel increased significantly after 4 h. In vitro, cytotoxic activity revealed that arbutin-hydrogel has no toxicity. Also, the cutaneous penetration investigation revealed that arbutin-hydrogel had a superior cutaneous accumulation (42.25 ± 0.30%) compared to plain gel (16.80 ± 0.33%). Also, physico-chemical specifications assay and solid state assessment were employed to assess of optimum formulation. Arbutin-hydrogel (60.9 ± 1.68%) inhibited melanin formation more effectively than arbutin solution. In addition, arbutin-hydrogel exhibited a more inhibitory impact on L-dopa auto-oxidation (54.90 ± 2.26%) than arbutin solution (38.62 ± 2.26%). In addition, the Wistar rat cutaneous sensitivity testing demonstrated that the hydrogel component did not affect the epidermis. These outcomes demonstrated that the arbutin-hydrogel could potentially be utilized for Arbutin topical delivery, expanding the treatment options for hyperpigmentation disorders. [ABSTRACT FROM AUTHOR]

Pelotherapy treatments in thermal spas, which utilize peloids composed of clay minerals mixed with saltwater or mineral-medicinal water, can have various effects on spa users, ranging from therapeutic to potential adverse reactions. Despite the widespread use of peloids, comprehensive information on the penetration and permeation of essential and potentially toxic elements into deeper layers of the skin during pelotherapy is limited. Understanding the concentrations of these elements is crucial for evaluating therapeutic benefits and ensuring safety. This study investigates the in vitro availability and absorption of calcium, magnesium, and potentially toxic elements in two peloids, considering their formulation matrix. To replicate the pelotherapy methodology, an in vitro permeation experiment was conducted using a vertical diffusion chamber (Franz cells) and a biological system with human skin membranes from five Caucasian women, age range between 25 and 51 years. The experiment involved heating the peloids to 45℃. The results emphasize the possible transport properties of chemical elements in peloids, providing valuable information related to potential therapeutic efficacy and safety considerations. Despite no apparent differences between peloids' chemical composition, the method identified permeation variations among chemical elements. The methodology employed in this study adheres to the guidelines outlined by OECD for analyzing skin absorption through an in vitro approach. Furthermore, it aligns with the associated OECD guidance document for conducting skin absorption studies. The replicability of this methodology not only facilitates the analysis of peloids pre-formulation but also provides a robust means to evaluate the effectiveness of therapeutic elements during topical administration, particularly those with potential toxicity concerns. [ABSTRACT FROM AUTHOR]

As the global facial mask market continues to grow, consumers have put forward higher requirements for the functionality and ingredients of mask products. Ordinary facial masks mostly use ordinary non-woven fabrics as the mask base fabric and are used with essence. Preservatives are generally added. At the same time, they are susceptible to the influence of the external environment and are easily oxidized, causing the mask to deteriorate and cause skin allergic reactions. In addition, traditional facial masks have problems such as poor fit with the skin, poor breathability, insufficient absorption of nutrient solutions, and easy dripping. The high specific surface area and high porosity of a nanofiber mask prepared by electrospinning technology are beneficial to the skin's absorption of nutrients, and it has good fit with the skin and strong breathability. A unique advantage of this nanofiber mask is that it uses spray. After the mask is sprayed with water or essence, the water-soluble polymer within it can be quickly dissolved, saving a lot of time. Nanofiber facial mask products can effectively solve consumer pain points and are conducive to the high-end development of facial masks. Therefore, this article combines needleless electrospinning technology to develop a new solid-state, preservative-free, quick-dissolving nanofiber facial mask that can be prepared on a large scale. Based on needleless electrospinning technology, this article deeply explores the process parameters and their influencing mechanisms for preparing nanofiber, quick-dissolving facial masks to achieve the stable preparation of nanofiber facial masks with the best morphology; a comprehensive analysis of the structure and influence of nanofiber facial masks from micro and macro perspectives demonstrates their performance and allows evaluation of them. The experimental results show that the mask morphology is optimal under the process conditions of using a spinning liquid of 20% collagen peptide solution, a spinning voltage of 30 kV, a collection distance of 19 cm, and a liquid supply speed of 130 mL/h. [ABSTRACT FROM AUTHOR]

In order to develop a novel biomedical dressing to promote wound healing, three types of drug-loaded microspheres were prepared using electrostatic spraying technology. Scanning electron microscopy, infrared spectroscopy, and hydrophilicity test were used to characterize the morphology, structure, and wetting properties of the microspheres, and the results showed that the three microspheres had the most suitable concentrations for loading drugs: 1% concentration of polylactic acid（PLA）,3% concentration of acrylic resin（PAR）,and 1% concentration of chitosan（CS),and that the three microspheres had good wetting and encapsulation effects. The skin adsorption experiments showed that the microspheres could be qualitatively analyzed to be indeed adsorbed on the skin surface, and further simulated the determination of microsphere loss rate in the natural environment, which quantitatively illustrated the adhesion of the microspheres on the skin surface. [ABSTRACT FROM AUTHOR]

When approving plant protection products, exposure data are required for risk analysis. Exposure data can be collected for various exposure pathways, such as dermal, inhalation or ground sediment. For measuring exposures, pyranine, a fluorescent dye, and a collector can be used. However, the choice of collector material depends on the specific exposure pathway. This study aims to determine the most suitable collector, in combination with the tracer pyranine, for recording exposure through different pathways in practical trials. Seven different collectors (Tyvek®, labels, plastic patches, paper patches, nylon filters, fibreglass filters, petri dishes) were subjected to laboratory and field tests to assess various quality parameters. Blank values, recovery rates, storability, and fluorescence degradation under UV-radiation were measured. Based on the results, a matrix was created summarizing which collector might be best suited to capture each exposure pathway. Almost all collectors demonstrated high recovery rates (Tyvek® 100%; labels 100%; plastic patches 100%; paper patches 100%; nylon filters 95%; fiberglass filters 60.9%) as well as good storability. Furthermore, all plastic-based collectors (labels, Tyvek®, plastic patches, petri dishes) showed a very good recovery rate above 95% when exposed to UV-radiation. However, nylon filters were not suitable for utilization under field conditions due to the rapid degradation of fluorescence under UV-radiation (recovery rate: 20–56%). Nevertheless, nylon filters showed stable recoveries under protected conditions and can be used to assess inhalation exposures under these conditions. Fibreglass filters, with recovery rates of 84–86%, were well-suited for testing inhalative exposures outdoors when a correction factor was applied. Tyvek® was the most suitable material for detecting total dermal exposure under field conditions. This is due to its quality characteristics and availability in a variety of sizes. Finally, petri dishes were ideal for collecting ground sediments. [ABSTRACT FROM AUTHOR]

Quantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp predictions from QSPR models. One proposed resolution involves using Kroes' methodology, categorizing DAs based on Kp values; however, refinement becomes necessary owing to discreteness in the obtained values. We previously developed a mathematical model using Kp values obtained from in vitro dermal absorption tests to predict DAs. The present study introduces a new methodology, Integrating Mathematical Approaches (IMAS), which combines QSPR models and our mathematical model to predict DAs for risk assessments without conducting in vitro dermal absorption tests. Regarding 40 chemicals (76.1 ≤ MW ≤ 220; -1.4 ≤ Log Ko/w o/w 3.1), IMAS showed that 65.0% (26/40) predictions of DA values were accurate to within twofold of the observed values in finite dose experiments. Compared to Kroes' methodology, IMAS notably mitigated overestimation, particularly for hydrophilic chemicals with water solubility exceeding 57.0 mg/cm3. These findings highlight the value of IMAS as a tool for skin product risk assessments, particularly for hydrophilic compounds. [ABSTRACT FROM AUTHOR]

Various cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood. To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated. There were considerable individual differences in epidermal CYP1A2 mRNA expression levels, and CYP1A2 showed a weak positive correlation with CYP3A4 mRNA expression levels. In contrast to previous results for other organs, epidermal CYP3A4 mRNA expression levels showed a weak positive correlation with BMI. CYP3A4 in the epidermis may have been locally enhanced as a defence mechanism against xenobiotics in response to impaired barrier function. These differences in mRNA expression in the skin may affect the transdermal absorption of drugs, such as lidocaine and fentanyl, which are metabolised by multiple overlapping CYPs. Our study provides new insights into drug metabolism in the skin. These results are valuable for predicting drug effects and transdermal drug transfer rates in Japanese patients. [ABSTRACT FROM AUTHOR]

The ongoing expansion of fifth-generation (5G) and future sixth-generation (6G) mobile communications is expected to result in widespread human exposure to millimeter-wave (mmWave) radiation globally. Given the short penetration depth of mmWaves and their high absorption by the skin, it is imperative to investigate the potential effects of 5G radiation not only in terms of temperature increase but also at the cellular level. To understand the biological mechanisms of mmWave effects, accurate methods for assessing mmWave absorption in the skin are crucial. In this study, we use fluorescence lifetime imaging microscopy (FLIM) to explore these effects. Employing a mmWave exposure system operating at 26 gigahertz (GHz), porcine skin is irradiated for varying durations (5, 10, 20, and 30 min). We investigate changes in tissue temperature and the autofluorescence of flavin adenine dinucleotide (FAD). Our findings suggest that operating our mmWave exposure systems at the configured power level of 26 GHz is unlikely to cause damage to FADs, even after a 30 min exposure duration. [ABSTRACT FROM AUTHOR]

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962–0.9993), accuracy (93.5–111.73%), and precision (1.7–14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 μL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 μg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 μg/cm2), respectively. [ABSTRACT FROM AUTHOR]

Plastic accumulation in the environment is rapidly increasing, and nanoplastics (NP), byproducts of environmental weathering of bulk plastic waste, pose a significant public health risk. Particles may enter the human body through many possible routes such as ingestion, inhalation, and skin absorption. However, studies on NP penetration and accumulation in human skin are limited. Loss or reduction of the keratinized skin barrier may enhance the skin penetration of NPs. The present study investigated the entry of NPs into a human skin system modeling skin with compromised barrier functions and cellular responses to the intracellular accumulations of NPs. Two in vitro models were employed to simulate human skin lacking keratinized barriers. The first model was an ex vivo human skin culture with the keratinized dermal layer (stratum corneum) removed. The second model was a 3D keratinocyte/dermal fibroblast cell co-culture model with stratified keratinocytes on the top and a monolayer of skin fibroblast cells co-cultured at the bottom. The penetration and accumulation of the NPs in different cell types were observed using fluorescent microscopy, confocal microscopy, and cryogenic electron microscopy (cryo-EM). The cellular responses of keratinocytes and dermal fibroblast cells to stress induced by NPs stress were measured. The genetic regulatory pathway of keratinocytes to the intracellular NPs was identified using transcript analyses and KEGG pathway analysis. The cellular uptake of NPs by skin cells was confirmed by imaging analyses. Transepidermal transport and penetration of NPs through the skin epidermis were observed. According to the gene expression and pathway analyses, an IL-17 signaling pathway was identified as the trigger for cellular responses to internal NP accumulation in the keratinocytes. The transepidermal NPs were also found in co-cultured dermal fibroblast cells and resulted in a large-scale transition from fibroblast cells to myofibroblast cells with enhanced production of α-smooth muscle actin and pro-Collagen Ia. The upregulation of inflammatory factors and cell activation may result in skin inflammation and ultimately trigger immune responses. [ABSTRACT FROM AUTHOR]

Mathematical models of epidermal and dermal transport are essential for optimization and development of products for percutaneous delivery both for local and systemic indication and for evaluation of dermal exposure to chemicals for assessing their toxicity. These models often help directly by providing information on the rate of drug penetration through the skin and thus on the dermal or systemic concentration of drugs which is the base of their pharmacological effect. The simulations are also helpful in analyzing experimental data, reducing the number of experiments and translating the in vitro investigations to an in-vivo setting. In this study skin penetration of topically administered caffeine cream was investigated in a skin-on-a-chip microfluidic diffusion chamber at room temperature and at 32°C. Also the transdermal penetration of caffeine in healthy and diseased conditions was compared in mouse skins from intact, psoriatic and allergic animals. In the last experimental setup dexamethasone, indomethacin, piroxicam and diclofenac were examined as a cream formulation for absorption across the dermal barrier. All the measured data were used for making mathematical simulation in a three-compartmental model. The calculated and measured results showed a good match, which findings indicate that our mathematical model might be applied for prediction of drug delivery through the skin under different circumstances and for various drugs in the novel, miniaturized diffusion chamber. [ABSTRACT FROM AUTHOR]

• Solvent deposition of dissolved solutes on human skin shows that spreading and evaporation rates and (possibly) osmosis govern dermal delivery. • At low doses, aqueous ethanol or dilute nonionic surfactants improve delivery versus water or ethanol alone without impacting the stratum corneum lipid barrier. • Authors recommend these excipients for finite dose testing of pharmaceutical and cosmetic ingredients. This study probes the mechanisms by which volatile solvents (water, ethanol) and a nonionic surfactant (Triton X-100) influence the skin permeation of dissolved solutes following deposition of small doses onto unoccluded human skin. A secondary objective was to sharpen guidelines for the use of these and other simple solvent systems for dermal safety testing of cosmetic ingredients at finite doses. Four solutes were studied – niacinamide, caffeine, testosterone and geraniol – at doses close to that estimated to saturate the upper layers of the stratum corneum. Methods included tensiometry, visualization of spreading on skin, polarized light microscopy and in vitro permeation testing using radiolabeled solutes. Ethanol, aqueous ethanol and dilute aqueous Triton solutions all yielded surface tensions below 36 mN/m, allowing them to spread easily on the skin, unlike water (72.4 mN/m) which did not spread. Deposition onto skin of niacinamide (32 μg·cm−2) or caffeine (3.2 μg·cm−2) from water and ethanol led to crystalline deposits on the skin surface, whereas the same amounts applied from aqueous ethanol and 2 % Triton did not. Skin permeation of these compounds was inversely correlated to the extent of crystallization. A separate study with caffeine showed the absence of a dose-related skin permeability increase with Triton. Permeation of testosterone (8.2 μg·cm−2) was modestly increased when dosed from aqueous ethanol versus ethanol. Permeation of geraniol (2.9 μg·cm−2) followed the order aqueous ethanol > water ∼ 2 % Triton >> ethanol and was inversely correlated with evaporative loss. We conclude that, under the conditions tested, aqueous ethanol and Triton serve primarily as deposition aids and do not substantially disrupt stratum corneum lipids. Implications for the design of in vitro skin permeability tests are discussed. [ABSTRACT FROM AUTHOR]

Pain is an unfavorable feeling that is generally triggered by endogenous or exogenous harmful stimulation and has a strong emotional impact. The objective of this experimentation was to increase the cutaneous absorption of nortriptyline HCl (NOR) encapsulated in a niosome (norosomes) produced by an ultrasonic approach for the management of antinociceptive and anti-inflammatory disorders. Exploring the implications of the cholesterol:surfactant ratio on norosome compositions, the study revealed that increasing cholesterol significantly enlarged the norosome diameter from 66.84 ± 5.70 to 293.06 ± 36.54 nm (p < 0.05). More research revealed that changes in the cholesterol:surfactant ratio could influence the surface charge (19.27 ± 0.89 to 16.30 ± 0.78 mV) and entrapment efficiency (EE%) (7.90 ± 1.59 to 87.44 ± 2.11%) (p < 0.05). The amorphous nature of NOR in the niosome was shown by solid-state research. The dermal absorption study revealed that NOR was present at larger levels in dermal layers (41.79 ± 2.38%) and the receiver area (28.67 ± 1.33%) for norosome gel than for NOR-Carbopol gel. The norosomal's cell safety was 84%, and the MTT study indicated a reduction in norosome cytotoxicity. The skin irritation analysis conducted on Wistar rats showed that the niosome component used did not cause irritation to the skin. Eventually, in comparison to the control group, norosome formulation demonstrated significant antinociceptive and anti-inflammatory (246.16 ± 53.60 s) actions in the late stage formalin test, tail-flick latency (5.18 ± 0.18 s), and hot plate latency (12.57 ± 1.78 s) (p < 0.05). These findings suggest that niosomes have the potential to enhance the effectiveness of NOR as an antinociceptive and anti-inflammatory agent by improving drug delivery to the targeted site. [ABSTRACT FROM AUTHOR]

Cyclic and linear siloxanes are compounds synthesized from silicon consisting of alternating atoms of silicone and oxygen [Si-O] units with organic side chains. The most common cyclic siloxanes are octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6), while the most common linear siloxanes are high molecular weight polydimethylsiloxanes (PDMS) and low molecular weight volatile linear siloxanes known as hexamethyldisiloxane (L2), octamethyltrisiloxane (L3), decamethyltetrasiloxane (L4), dodecamethylpentasiloxane (L5). These compounds (1) exhibit low dermal toxicity, (2) are generally inert and non-reactive, and (3) are compatible with a wide range of chemicals offering beneficial chemical properties which include the following: wash-off or transfer resistance from the skin, sun protection factor (SPF) enhancement, emolliency in cleaning products). Because of these properties, these compounds are incorporated into multiple consumer products for use on the skin, such as cosmetics and health-care products, with over 300,000 tons annually sold into the personal care and consumer products sector. Because of their widespread use in consumer products and potential for human dermal exposure, a comprehensive understanding of the dermal absorption and overall fate of siloxanes following dermal exposure is important. This review summarizes available data associated with the dermal absorption/penetration as well as fate of the most commonly used siloxane substances. [ABSTRACT FROM AUTHOR]

Nanoemulsions represent a remarkable class of colloidal systems that play a pivotal role in the encapsulation, protection, and targeted delivery of active ingredients to the skin. One of the primary objectives in skincare science is to maximize the interaction between the active ingredients and the skin. This can be achieved through various mechanisms, two of which are occlusion and extended contact of the formulation with the skin. Cosmetic masks can be used to improve the skin's hydration by creating a barrier that minimizes transepidermal water loss while acting as a repository of the active ingredient, increasing the skin's absorption of the formulation's active ingredients. In order to diminish the environmental impact, natural-polymeric-material masks are being used, as an alternative to synthetic materials, for its biocompatibility and biodegradability. In this work pectin and tapioca starch were used to develop a polymeric mask to deliver a rice bran oil nanoemulsion and study some characteristics of the final product. The results show that the association of pectin and tapioca starch can be used to produce a film that can be molded and shows occlusive effects, besides being flexible and compatible with the skin. [ABSTRACT FROM AUTHOR]

Pesticides must not pose unacceptable risks to human health, so risk assessments are conducted before products are authorised. Dermal exposure is often the main route of intake, so estimating realistic and trustworthy dermal absorption values is crucial for risk assessment. Although there are agreed test guidelines for in vitro dermal absorption studies, not every product is tested due to cost reasons. The present dataset consists of 945 individual in vitro experiments on the dermal absorption of human skin with 179 active substances of pesticides in 353 different mixtures, including concentrates and dilutions. The dataset was evaluated to identify the possible impacts of experimental conditions and physico-chemical properties on dermal absorption. The dataset was also analysed to assess the appropriateness of the pro rata correction for untested dilutions, and the set concentration cut-off to decide on the dilution status for choosing a default value on dermal absorption. The study found that the implementation of specific guidelines improved the harmonisation of study conduct, with support for approaches such as pro rata correction and default values. Further analysis of the specific co-formulants may identify influencing factors that may be more important than the experimental variables. [ABSTRACT FROM AUTHOR]

ObjectiveCompare the relevance of flow-through versus static diffusion cells data as relates to bioequivalence.MethodsSearch was conducted on PubMed and Google Scholar. Keywords utilized: static cells, flow-through cells, percutaneous permeation, percutaneous absorption, dermal absorption, and types of permeation.ResultsFifteen articles were identified with no consistent significant differences between flow-through and static diffusion cells identified; any differences could exist for two main reasons. (1) Sampling time differences and (2) physical chemistry (lipophilic vs hydrophilic) of the penetrant examined.ConclusionEven though there was no consistent significant difference observed, labs have generally adapted to the method they regularly use, which is usually stated in their respective articles. Well-designed multicentered prospective comparative experiments should clarify potential advantages and disadvantages for each. For flow-through systems, the flow rate that most approximates to comparable in vivo data for animals and humans may be preferable.

Background: Niosomes hold promise as drug delivery systems for cancer treatment, with niosome size impacting stability, biodistribution, and effectiveness. This study optimized methotrexate (MTX)-loaded niosome formulation by studying the effects of components and processing conditions on size. The niosomes formulation was made by the thin-film hydration technique. Results: The optimized formulation (NIO 17) with a 6:2:2 ratio of span 60, soya PC, and cholesterol achieved 55.05% methotrexate encapsulation, particle size 597.2 nm, PDI 0.49, and zeta potential − 23.3 mV. The compatibility of methotrexate with lipids was confirmed via Fourier transform infrared spectroscopy, and transmission electron microscopy revealed spherical, well-dispersed vesicles. Differential scanning calorimetry indicated methotrexate conversion or entrapment within vesicles. In vitro release exhibited a sustained pattern with an initial burst. NIO 17 showed potent anti-cancer activity against B16-F10 cells (GI50: 38.7176 μg/mL). Ex vivo studies suggest tailoring niosome size (597.2–982.3 nm) to target specific skin depths (0–38 μm) for enhanced localized drug delivery. Conclusions: This study demonstrates the potential of methotrexate-loaded niosomes as a novel cancer therapy approach, highlighting the potent anti-cancer activity and transdermal delivery potential of NIO 17. Further research is necessary to explore its clinical translation. [ABSTRACT FROM AUTHOR]

Given the broad and intense use of plastic, society is being increasingly affected by its degradation and by-products, particularly by microplastics (MPs), fragments smaller than 5 mm in size, and nanoplastics (NPs), with sizes less than 1 µm. MPs and NPs may enter the body primarily through inhalation, consumption, and skin contact. Once ingested, MPs can penetrate tissues, deviating to other parts of the body and potentially affecting important cellular pathways such as nonconforming chemokine receptors that control the communication between the fetus and the mother. Consequently, the potential health harm induced via MP internalization is a major issue, evidenced by multiple studies demonstrating harmful consequences in diverse animal models and human cells. Here, an overview of the various modes of exposure to MPs and NPs is presented, including inhalation, placental transfer, ingestion, breastmilk consumption, and skin absorption, as well as placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Though MPs in our environment are becoming more recognized, their developmental toxicity is still scarcely known. Besides negatively affecting pregnancy, MPs and NPs have been shown to potentially harm the developing fetus, given their ability to cross the placental barrier. Still, considerable gaps remain in our understanding of the dispersion and toxicity of these particles in the environment and the precise types of NPs and MPs bearing the greatest dangers. As a result, we advocate for larger-scale epidemiological investigations, the development of novel approaches for measuring NP and MP exposures, and the necessity of understanding the toxicity of various kinds of NPs to guide future research efforts. [ABSTRACT FROM AUTHOR]

Human skin acts as a protective barrier, preserving bodily functions and regulating water loss. Disruption to the skin barrier can lead to skin conditions and diseases, emphasizing the need for skin hydration monitoring. The gold-standard sensing method for assessing skin hydration is the Corneometer, monitoring the skin's electrical properties. It relies on measuring capacitance and has the advantage of precisely detecting a wide range of hydration levels within the skin's superficial layer. However, measurement errors due to its front end requiring contact with the skin, combined with the bipolar configuration of the electrodes used and discrepancies due to variations in various interfering analytes, often result in significant inaccuracy and a need to perform measurements under controlled conditions. To overcome these issues, we explore the merits of a different approach to sensing electrical properties, namely, a tetrapolar bioimpedance sensing approach, with the merits of a novel optical sensing modality. Tetrapolar bioimpedance allows for the elimination of bipolar measurement errors, and optical spectroscopy allows for the identification of skin water absorption peaks at wavelengths of 970 nm and 1450 nm. Employing both electrical and optical sensing modalities through a multimodal approach enhances skin hydration measurement sensitivity and validity. This layered approach may be particularly beneficial for minimising errors, providing a more robust and comprehensive tool for skin hydration assessment. An ex vivo desorption experiment was carried out on fresh porcine skin, and an in vivo indicative case study was conducted utilising the developed optical and bioimpedance sensing devices. Expected outcomes were expressed from both techniques, with an increase in the output of the optical sensor voltage and a decrease in bioimpedance as skin hydration decreased. MLR models were employed, and the results presented strong correlations (R-squared = 0.996 and p-value = 6.45 × 10−21), with an enhanced outcome for hydration parameters when both modalities were combined as opposed to independently, highlighting the advantage of the multimodal sensing approach for skin hydration assessment. [ABSTRACT FROM AUTHOR]

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype–phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val). Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype–phenotype correlations are needed. [ABSTRACT FROM AUTHOR]

The use of pesticide in modern agriculture and public health sector has been increased tremendously. Only 0.1% of pesticide applied to crops truly reaches the target, the rest of it enters into the environment. Several pesticides can persist in an ecosystem for longer periods accumulate in the body tissues of organisms and cause more health problems. Pesticide exposure generally occurs through ingestion, inhalation and skin contact or absorptions by intentionaly or unintentionaly which leads to acute and chronic health problems in non target organisms such as animals, birds, aquatic animals and human. A total of more than 100 articles related to impact of pesticide exposure were reviewed. To review the literature, we reviewed a number of studies, report and abstract between 1950 to 2020 using key words effect of pesticide on animals, birds, human, environment we used this term to search in in PubMed, ResearchGate and google scholar. Searching strategy also include cross-referencing of research and review article Improving epidemiological studies, metabolic studies, residue monitoring and experimental research on pesticide exposure can reduces human health risks of pesticide exposure. This article clearly explains how the pesticide enter into the atmosphere, soil and water and its adverse effect on birds, animals and human, major incidence regarding pesticide exposure and effort should be taken prevent the pesticide poisoning. [ABSTRACT FROM AUTHOR]

The evaluation of drug percutaneous absorption plays a pivotal role in assessing the efficacy of dermal/transdermal drug delivery systems. Drug therapies rely on biomedical systems capable of precisely regulating drug dosage, controlling the rate of drug release, and mitigating the common side effects associated with many drug delivery formulations. Pluronics are being broadly used as amphiphilic excipients in many drug delivery systems due to their capacity to create supramolecular assemblies in water, exhibiting significant potential for sustained drug delivery. We herein report on the release kinetics of diclofenac sodium contained in novel biocompatible drug delivery systems consisting of aqueous solutions of Pluronic F68. The latter is tested as a release vehicle for percutaneous administration of diclofenac sodium. Its release from Pluronic F68 nanoassemblies in water was experimentally examined by means of a static Franz-type diffusion cell, equipped with a porous membrane simulating the skin absorption, and supported by rheology. Furthermore, the drug release process was modeled through a mass balance for the diclofenac sodium describing its diffusion in pseudostationary conditions through the porous membrane. [ABSTRACT FROM AUTHOR]

Background: Ketoprofen is a nonsteroidal anti‐inflammatory drug used for the treatment of acute and chronic pain associated with inflammatory conditions. This study aims to evaluate the in vitro percutaneous absorption of ketoprofen 10% formulated in proprietary anhydrous and aqueous gels using the Franz skin finite dose model. Materials and Methods: The anhydrous gel was initially characterized for cytotoxicity using EpiDerm skin tissue model by cell proliferation assay and Western blot analysis. The Ultra Performance Liquid Chromatography method for measuring ketoprofen was validated and the stability of ketoprofen 10% in the anhydrous gel formulation was evaluated at 5°C and 25°C for 181 days. The percutaneous absorption of ketoprofen was determined using donated human skin. The tissue sections were mounted within Franz diffusion cells. A variable finite dose of each ketoprofen formulation in either anhydrous or aqueous gel was applied to the skin sections and receptor solutions were collected at various time points. Results: Cell proliferation assay showed minimal cell death when EpiDerm skin tissue was exposed to the anhydrous gel for 24 h; the levels of protein markers of cell proliferation were not affected after 17‐h exposure. Ketoprofen was stable in the anhydrous gel when stored at 5°C and 25°C. When compounded in the anhydrous and aqueous gels, ketoprofen had mean flux rate of 2.22 and 2.50 μg/cm2/h, respectively, after 48 h. The drug was distributed to the epidermis and dermis sections of the skin. Both the anhydrous and aqueous gels facilitated the percutaneous absorption of ketoprofen without statistically significant differences. Conclusion: The anhydrous gel can be used as a base to facilitate the transdermal delivery of ketoprofen. Although the anhydrous and aqueous gels can deliver a similar amount of ketoprofen, the anhydrous gel (water activity below 0.6) allows for extended default beyond‐use‐date of compounding preparations. [ABSTRACT FROM AUTHOR]

Ethylhexyl methoxycinnamate (EHMC) is frequently employed as a photoprotective agent in sunscreen formulations. EHMC has been found to potentially contribute to health complications as a result of its propensity to produce irritation and permeate the skin. A microgel carrier, consisting of poly(ethylene glycol dimethacrylate) (pEDGMA), was synthesized using interfacial polymerization with the aim of reducing the irritation and penetration of EHMC. The thermogravimetric analysis (TGA) indicated that the EHMC content accounted for 75.72% of the total composition. Additionally, the scanning electron microscopy (SEM) images depicted the microgel as exhibiting a spherical morphology. In this study, the loading of EHMC was demonstrated through FTIR and contact angle tests. The UV resistance, penetration, and skin irritation of the EHMC-pEDGMA microgel were additionally assessed. The investigation revealed that the novel sunscreen compound, characterized by limited dermal absorption, had no irritant effects and offered sufficient protection against ultraviolet radiation. [ABSTRACT FROM AUTHOR]