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This study introduces an innovative approach to enhance the absorption capabilities of skin‐core dual‐domain structure radar‐absorbing materials (SDSRAM) composed of thin‐ply laminates and honeycomb. The upper skin laminates consist of transmissive skin and impedance matching layer. The impedance matching layer was hot‐pressed using functionalized absorbed thin‐ply glass fibers prepregs, flaked carbonyl iron powder (FCIP) and multi‐walled carbon nanotubes (MWCNTs) as the absorber. The lower skin was manufactured using carbon fiber‐plated nickel. The core is prepared by honeycomb modified (HCM). The permittivity and permeability of the skin laminates and the HCM were measured by wave‐guide method. The impact of FCIP/MWCNT on the electromagnetic (EM) parameters of the thin‐ply laminates and the influence of MWCNTs on the permittivity of the honeycomb were investigated. Microwave absorption properties of SDSRAM were assessed through the measurement of reflection loss (RL) using the arch method and simulated using the microwave simulation software CST studio suite 2020. Experimental verification was conducted to confirm the absorbing performance. The results show that the effective absorption bandwidth (RL < 10 dB) of SDSRAM covers the frequency range of 2.2–18 GHz, with a maximum absorption intensity of −42.5 dB. The introduction of the thin‐ply laminates caused a shift in the peak of the reflectance curve toward lower frequencies. Highlights: Functionalized absorbed glass fibers were prepared using fiber spreading functional sizing integrated process.A new skin‐core dual‐domain synergistic modulation absorbed structure was developed with thin‐ply laminates and modified honeycomb. Its broadband absorption mechanism was discussed.Desired broadband absorption performance was acquired with thin thickness. [ABSTRACT FROM AUTHOR]

Magnetoresistance (MR), magnetoinductance (mi), and magnetoimpedance (MI) studies on the as-quenched and annealed Fe72Si10Cu1Nb2B15, Co72Ni5Si5Cu1Nb2B15, and Co77Si5Cu1Nb2B15 ribbons have been carried out in the present investigation. Structural studies indicate that all as-quenched samples are in the amorphous phase. The asymmetry in the MI, MR, and mi curves is noticed and is attributed to induced magnetocrystalline anisotropy and hysteretic magnetization. Among all three samples, the Co77Si5Cu1Nb2B15 ribbons exhibit the highest magnetization and MI values. The development of a strong transverse magnetic anisotropy upon annealing has been observed in the Co77Si5Cu1Nb2B15 ribbons, while such features are not observed in other cases. The present study shows that 5% Ni substitution in Co77Si5Cu1Nb2B15 samples significantly reduces the transverse anisotropy, indicating that the transverse anisotropy can be tuned through Ni substitution. [ABSTRACT FROM AUTHOR]

As a natural bioactive compound, curcumin (Cur) has traditionally used for various therapeutic purposes, but due to low solubility, poor skin permeability, and the possibility of superficial staining, its topical applications is restricted. Thus, this study aimed to develop a topical formulation, increasing the solubility of Cur and promoting potential applications. In this context, Cur nanoemulsions were prepared through continuous emulsification and optimized with different ratios of components to achieve desirable properties and superior encapsulation. Accordingly, nanoemulsions prepared by the oleic acid (10%w/w) as oil phase, PEG 400 (6%w/w) as co-surfactant and mixture of Tween 80® and Span 80® (8%w/w) as surfactant showed the most favorable properties with a droplet size of 12.26 nm and polydispersity index (PDI) of 0.254. Afterward, the optimized formulation was converted to nanoemulgel using 1%w/w of Carbopol 940. The Cur formulation presented good physiochemical properties in terms of uniformity, thermodynamic stability, spreadability, and droplet size. The results showed that the release profile follows the Higuchi kinetic model. Moreover, this formulation presented excellent antioxidant capacity (FRAP value of 533.49 ± 2.84 µM Fe (II)/g) and potential photoprotective efficacy (SPF value of 13.86). It was also found to have high anti-inflammatory properties and antibacterial activity (250 µg/ml ≤ MIC < 500 µg/ml) against Staphylococcus aureus and Escherichia coli. According to the results, the current formulation of Cur is a promising candidate to improve the solubility and promote its efficacy for various topical applications. [ABSTRACT FROM AUTHOR]

The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds. [ABSTRACT FROM AUTHOR]

Despite its long history as a preferential cyclooxygenase-2 inhibitor, the topical application of etodolac in inflammatory disorders does not achieve the desired clinical efficiency because of its poor water solubility and poor skin permeation. In the ongoing study, phosalosomes were designed to mitigate the etodolac drawbacks and to enhance its skin localization. Hyaluronic acid was utilized to prepare a dermal gel for the alleviation of skin inflammation. Etodolac loaded hyaluronic acid phosalosomal gel had a sustainable release profile and 10.59-fold enhanced skin retention compared to free etodolac, with boosted skin tolerability on histopathological examination after acute and chronic applications. Confocal laser microscopy imaging indicated that the etodolac amounts accumulated in the liver and kidney following dermal application were 29 and 5.7-fold lower than those following the systemic dose, respectively. For in vivo studies, etodolac loaded hyaluronic acid phosalosomal gel presented superior anti-oedemic and significant anti-nociception potential. The promising homogenous localization highlighted its potential for the delivery of lipophilic drugs for the targeted treatment of other localized skin disorders. [ABSTRACT FROM AUTHOR]

Traditional sunscreens, especially organic ultraviolet (UV) absorbers such as benzophenone, have strong photoactivity and skin permeability, which may cause some human injuries and even cancer. Therefore, it is of great practical significance to develop efficient and safe new sunscreen. With anhydrous zinc acetate (Zn(Ac)2), titanium tetrachloride (TiCl4) and dopamine hydrochloride as raw materials and ethanol/water solution as solvent, polydopamine (PDA) coated Zn-Ti layered double hydroxide (P@ZTL) compounded particles were synthesized through a hydrothermal method. Afterwards, sunscreen samples were prepared with them as the only UV-blocking component. The chemical structure, composition and micro- morphology, along withUV absorbance, free radical scavenging and cytotoxicity performance of P@ZTL were studied. Indispensably, the UV-blocking properties of the sunscreen samples were tested. The results showed that the structure of P@ZTL was 1~5 μm PDA coated ZTL compounded particles, with a specific surface area of 145. 916 m2/g. The particles had a typical mesoporous structure with a porosity of 0. 154 cm3/g. The compounded particles had great UV absorption and reactive oxygen species(ROS)scavenging abilities, along with no cytotoxicity. The sunscreen with P@ZTL had excellent UV protecting performance, which could preserve fibroblasts from direct UV irradiation. The sun protection index(SPF)values of sunscreen samples added with 10% and 15% P@ZTL reached 47. 3±2. 3 and 75. 1±3. 1, respectively, which could fully meet the daily use. Therefore, the synthesized P@ZTL sunscreen has a great application prospect in cosmetics. [ABSTRACT FROM AUTHOR]

Little is known about how sun exposure may affect the maternal skin barrier during pregnancy when many hormonal and physiological changes occur. In this longitudinal observational study, 50 pregnant women were recruited at 18–24 weeks' gestation, 25 in summer–autumn, and 25 in winter–spring. At three time points in pregnancy at 18–24, 28–30, and 36–38 weeks' gestation, participants completed a validated sun exposure questionnaire and had skin permeability and surface pH measured on the volar forearm. We identified an association between increased sun exposure and increased skin permeability at 18–24 weeks' gestation (β = 0.85, p = 0.01). Lower transepidermal water loss (decreased skin permeability), mean = 12.1 (SD = 5.1) at 28–30 weeks' gestation was observed, compared to mean = 12.6 (SD = 4.0) at 18–24 weeks' and mean = 13.7 (SD = 8.5) at 36–38 weeks' gestation (n = 27, β = −1.83, p = 0.007). Higher skin pH readings, mean = 5.80 (SD = 0.58) were found at 28–30 weeks' gestation, compared to mean = 5.25 (SD = 0.62) at 18–24 weeks' and mean = 5.47 (SD = 0.57) at 36–38 weeks' gestation (n = 27, β = 0.40, p = 0.004). These gestational fluctuations remained after adjusting for Fitzpatrick skin type, season, and sun exposure. We observed gestational fluctuations in both skin permeability and skin pH, with 28–30 weeks' gestation being a significant point of difference compared to mid‐ and late‐pregnancy periods. [ABSTRACT FROM AUTHOR]

Phycocyanin (PC) is a naturally occurring green pigment in Spirulina. It was extracted by ultrasonic extraction using green technology, and its structure was studied using IR- and NMR-spectroscopy. Spectral data confirmed the PC structure. This study also involves an in silico assessment of the diverse applications of green pigment PC. Utilizing QSAR, PreADME/T, SwissADME, and Pro-Tox, this study explores the safety profile, pharmacokinetics, and potential targets of PC. QSAR analysis reveals a favorable safety profile, with the parent structure and most metabolites showing no binding to DNA or proteins. PreADME/T indicates low skin permeability, excellent intestinal absorption, and medium permeability, supporting oral administration. Distribution analysis suggests moderate plasma protein binding and cautious blood–brain barrier permeability, guiding formulation strategies. Metabolism assessments highlight interactions with key cytochrome P450 enzymes, influencing drug interactions. Target prediction analysis unveils potential targets, suggesting diverse therapeutic effects, including cardiovascular benefits, anti-inflammatory activities, neuroprotection, and immune modulation. Based on the in silico analysis, PC holds promise for various applications due to its safety, bioavailability, and potential therapeutic benefits. Experimental validation is crucial to elucidate precise molecular mechanisms, ensuring safe and effective utilization in therapeutic and dietary contexts. DFT calculations, including geometry optimization, MEP analysis, HOMO-LUMO energy surface, and quantum reactivity parameters of the PC compound, were obtained using the B3LYP/6–311G(d,p) level. This integrated approach contributes to a comprehensive understanding of PC's pharmacological profile and informs future research directions. [ABSTRACT FROM AUTHOR]

The article describes the groundbreaking new ingredient Shiloxome ™, developed by Provital, which counteracts signs of aging and protects the skin in a multi-omic way. The ingredient is derived from the endophytic yeast Kwoniella mangroviensis and acts as a protective shield for the skin. Provital has developed a technology that allows them to isolate endophytic strains and investigate their bioactivity. The first developed ingredient, Shiloxome ™, comes from the endophytic yeast species Kwoniella mangroviensis found in the bark of the cork oak. This ingredient protects the skin and gives it the ability to adapt and survive. Provital has also conducted a study on the effectiveness of the ingredient, which has shown that it protects the skin from environmental stressors and improves the integrity of the skin barrier. The active ingredient has a positive effect on the overall chain length of the lipidome and strengthens the permeability barrier of the skin. Signal pathways related to the structure and organization of the extracellular matrix have been identified. The active ingredient also has a significant effect on the remodeling and overall condition of the skin structure and function. An improvement in elastin and collagen I levels has been observed. The results show that the active ingredient strengthens the lipid barrier and contributes to the restoration of youthful and healthy skin. The article describes a new active ingredient called Shiloxome ™, developed by Provital. The active ingredient is based on endophytes and is produced using the Triplobiome ™ technology. Shiloxome ™ offers benefits in the fight against skin aging and restructures the skin barrier. It has been shown that the active ingredient reduces lipid oxidation and provides comprehensive skin protection. Shiloxome ™ is recommended as a powerful ally for resilient, youthful skin. [Extracted from the article]

The frequent use of anti‐inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen‐like compounds, which are frequently used anti‐inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti‐inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX‐1 enzyme with an IC50 = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies. [ABSTRACT FROM AUTHOR]

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. [ABSTRACT FROM AUTHOR]

Melatonin's antioxidant properties make it a valuable component in anti-aging semisolid topical products. This study explores the role of Pemulen®, an acrylic-based viscosifying agent, in stabilizing cream-gel formulations. Remarkably, even at low concentrations (0.4%), Pemulen® successfully produced physicochemical stable topical formulations. In this work, the impact of the ratio of the oily phase—comprising olive oil and isopropyl myristate from 0 to 20%—was investigated to understand the internal microstructure effect on skin permeability, rheological properties, and stability. The formulations exhibited pseudoplastic behavior, with a significant positive correlation (p-value < 0.1) between the oily phase ratio, viscosity, spreadability, skin adhesiveness, and permeability. Formulations without the oil phase exhibited greater skin permeability. However, higher oily phase content enhanced viscosity, spreadability, and skin adhesion. Given that melatonin primarily degrades through oxidation, incorporating antioxidant excipients in semisolid formulations is crucial for maintaining its chemical stability. A quality by design (QbD) approach was used to assess the impact of four excipients—(a) DL-α-tocopheryl acetate (0.05%), (b) ascorbic acid (0.1%), (c) ethylene diamine tetraacetic acid (0.1%), and (d) sodium metabisulphite (0.5%)—on melatonin's stability. Our findings indicate that maintaining the physical stability of the formulation with a 20% oil phase is more critical for protecting melatonin from oxidation than merely adding antioxidant excipients. [ABSTRACT FROM AUTHOR]

Background: The present study aims to enhance the wound healing potential of the seed oil (SO) of Lagenaria siceraria (Egyptian cultivar) via the preparation of SO-loaded binary nanoethosomal (SO-BNE) gels. SO-BNEs were prepared using 23 factorial design, characterized for vesicle size, zeta potential, polydispersity index, linoleic and oleic acid EE% for ensuring improved skin permeability. The L. siceraria SO, optimized SO-BNE gels (0.5% and 5%) and Mebo® were topically applied in full-thickness wounded rat model twice daily for 10 days. Results: In the SO-BNE gel groups, the normal appearance of the skin architecture and structure of the dermis was revealed. In addition, the levels of NRF2, TGF-β1 and FOXO1, collagen type I, SMA-α and MIP2 were significantly elevated. The wound healing potential of SO-BNE gels was proposed to be via suppression of oxidative stress and stimulation of skin regeneration biomarkers. Furthermore, the SO screening through GC/MS unveiled high percentages of unsaturated fatty acids. SO was also found to be nontoxic to human skin fibroblast cells; enhanced viability and migration rates at concentration of 50 g/mL by 99.76% and 75.9%, respectively. Conclusion: These findings demonstrate that the Lagenaria siceraria SO-loaded BNE gels represent a promising delivery for wound healing with enhanced release and bioavailability. [ABSTRACT FROM AUTHOR]

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism. [ABSTRACT FROM AUTHOR]

Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza, has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrierfree pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both in vitro and in vivo anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-α, IL-1 β and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment. [ABSTRACT FROM AUTHOR]

Ceramide 2 is the main lipid of stratum corneum and a popular component in skin healthcare products. But developing ceramide 2 based corneal protecting product is troublesome due to its insoluble feature in water. In this work, a novel type of inclusion nanoparticle was developed to solubilize and enhance the corneal repair effect of ceramide 2 by the anti-solvent method. It was revealed that the types of solvents and cyclodextrins influenced the precipitation rate as well as the stability of intermediate clusters of ceramide 2, where DMSO with moderate supersaturation promoted the formation of inclusion complex with β-cyclodextrins. The ceramide-cyclodextrin inclusion complex had an amphiphilic structure, which could self-assemble into nanoparticles in water, as evidenced by disappeared endothermic peaks of ceramide (78°C) and cyclodextrin (120°C), as well as appearance of two endothermic peaks corresponding to nanoparticle transition (45°C) and dissociation of cyclodextrin inclusion complex (102°C). Upon treating rat damaged skins with ceramide 2 inclusion nanoparticles, the cumulative permeation of indomethacin (IND, a model drug for skin permeability) were found to be 330.80 ± 54.86 μg/cm2, which was significantly lower than the control group (472.47 ± 154.83 μg/cm2). In comparison, water suspensions of ceramide 2 showed no corneal repair effect. [ABSTRACT FROM AUTHOR]

Coalbed methane (CBM) productive efficiency and coal mine disasters such as gas outbursts and water inrush are closely correlated with coal seam permeability. Effective prediction of coal seam permeability can provide guidance for CBM production and prevention of coal mine disasters. In this research, a hybrid neural network prediction model integrating a genetic algorithm, an adaptive boosting algorithm, and a back propagation neural network was developed to predict coal seam permeability. Additional momentum and variable learning rate algorithms were used to improve the learning rate and accuracy of the model, and the model structure was optimized, including the number of hidden layer nodes and the transfer function. The input parameters of the prediction model included gas pressure, compressive strength, reservoir temperature, and effective stress. The corresponding output parameter was coal seam permeability. The correlation between the parameters was calculated. Additionally, a comparative analysis between the proposed prediction model and four other prediction models was carried out to demonstrate the advantages of the proposed model. The results indicated that the correlations between compressive strength, gas pressure, reserve temperature, effective stress, and coal seam permeability were 0.334, −0.148 , −0.406 , and −0.785 , respectively. The proposed prediction model had high accuracy compared with the other prediction models, and its coefficient of determination and root mean squared error were 0.999 and 0.021. Thus, the model can predict coal seam permeability more accurately. [ABSTRACT FROM AUTHOR]

Given the increasing aging population and the rising prevalence of musculoskeletal diseases due to obesity and injury, urgent research is needed to formulate new treatment alternatives, as current options remain inadequate. Viruses can exacerbate arthritis and worsen symptoms in patients with pre-existing osteoarthritis. Over the past decade, the chikungunya virus (CHIKV) has emerged as a significant public health concern, especially in Asia and South America. Exploring natural products, such as berberine, has shown promise due to its anticatabolic, antioxidative, and anti-inflammatory effects. However, berberine's low stability and bioavailability limit its efficacy. We hypothesized that encapsulating berberine into a proniosome gel, known for its ease of preparation and stability, could enhance its bioavailability and efficacy when applied topically, potentially treating CHIKV infection. Our investigation focused on how varying berberine loads and selected excipients in the proniosome gel influenced its physical properties, stability, and skin permeability. We also examined the biological half-life of berberine in plasma upon topical administration in mice to assess the potential for controlled and sustained drug release. Additionally, we analyzed the antioxidant stress activity and cell viability of HaCaT keratinocytes and developed a lipopolysaccharide-stimulated cell culture model to evaluate anti-inflammatory effects using pro-inflammatory cytokines. Overall, the research aims to transform the treatment landscape for arthritis by leveraging berberine's therapeutic potential. [ABSTRACT FROM AUTHOR]

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes. [ABSTRACT FROM AUTHOR]

Rutin, a flavonoid found in various plants, has gained attention for its potential applications in the cosmetic industry due to its antioxidant, anti-inflammatory, and potential photoprotective properties. Our review explored the use of rutin (rutoside, 3-O-rutinoside-quercetin) in cosmetics/dermocosmetics, focusing on its physicochemical properties and stability, cutaneous permeability, and efficacy in sunscreen systems, involving in vitro tests and the current state of clinical trials. Rutin's ability to scavenge free radicals, prevent peroxidation, and reduce vascular fragility makes this flavonoid a promising ingredient for photoprotection. Studies have shown that rutin can enhance the sun protection factor (SPF) of sunscreen formulations, especially when combined with organic UV filters. The encapsulation of rutin in nanostructures has also been investigated to improve its applicability. Overall, rutin shows potential as a safe and effective ingredient in cosmetics/dermocosmetics, offering protection against the harmful effects of UV radiation and oxidative stress on the skin, as well as being a feasible strategy for developing environmentally friendly multifunctional sunscreens. [ABSTRACT FROM AUTHOR]

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs. [ABSTRACT FROM AUTHOR]

Noninvasive mapping of cellular pathology can provide critical diagnostic and prognostic information. Recent advances in diffusion magnetic resonance imaging enabled in vivo examination of tissue microstructures well beyond the imaging resolution. Here, we proposed to use diffusion time-dependent diffusion kurtosis imaging (tDKI) to simultaneously assess cellular morphology and transmembrane permeability in hypoxic-ischemic (HI) brain injury. Through numerical simulations and organoid imaging, we demonstrated the feasibility of capturing effective size and permeability changes using tDKI. In vivo MRI of HI-injured mouse brains detected a shift of the tDKI peak to longer diffusion times, suggesting swelling of the cellular processes. Furthermore, we observed a faster decrease of the tDKI tail, reflecting increased transmembrane permeability associated with up-regulated water exchange or necrosis. Such information, unavailable from a single diffusion time, can predict salvageable tissues. Preliminary applications of tDKI in patients with ischemic stroke suggested increased transmembrane permeability in stroke regions, illustrating tDKI's potential for detecting pathological changes in the clinics. [ABSTRACT FROM AUTHOR]

Background: Microneedles are tiny needles, typically ranging from tens to hundreds of micrometers in length, used in various medical procedures and treatments. The tested medical device named "CELLADEEP Patch" a dissolvable microneedle therapy system (MTS), made of hyaluronic acid and collagen. And the iontophoresis technique is also applied in the system. The study aimed to evaluate the effectiveness of the "CELLADEEP Patch" in skin improvement. Methods: Ex vivo human‐derived skin tissue models were used in this study and they were divided into three different groups, namely, the Untreated Group, the Negative Control Group, and the Test Group respectively. The Untreated Group received no treatment measures, the Negative Control Group was exposed to ultraviolet B radiation (UVB) irradiation, and the Test Group was exposed to UVB irradiation and treated with "CELLADEEP Patch". Skin moisture content, transdermal water loss, and skin elasticity were evaluated by three clinical devices. Additionally, histological staining and related mRNA expression levels were also analyzed. Results: The results of skin moisture content, transdermal water loss, and skin elasticity evaluation consistently illustrated that the application of "CELLADEEP Patch" led to remarkable skin improvement. And the analysis of histological staining images also confirmed the effectiveness of the "CELLADEEP Patch", especially for increasing collagen density. Moreover, the upregulation of Collagen type 1 a (COL1A1) and hyaluronan synthase 3 mRNA expression and the decrease of Matrix metalloproteinase 1 (MMP‐1) and Interleukin‐1 beta (IL‐1β) mRNA expression reflected its wrinkle improvement, moisturizing and anti‐inflammation function. Conclusion: "CELLADEPP Patch", the MTS combined with the iontophoresis technique, exhibits its effectiveness in moisturizing, skin elasticity improvement, and anti‐inflammatory function when applied to ex vivo human‐derived skin tissue models in experiments. The study has contributed to the understanding of the "CELLADEPP Patch" and laid the foundation for subsequent animal experiments and clinical trials. [ABSTRACT FROM AUTHOR]

Wound healing of the central nervous system (CNS) is characterized by the classical phases of 'hemostasis', 'inflammation', 'proliferation', and 'remodeling'. Uncontrolled wound healing results in pathological scar formation hindering tissue remodeling and functional recovery in the CNS. Initial blood protein extravasation and activation of the coagulation cascade secure hemostasis in CNS diseases featuring openings in the blood-brain barrier. However, the relevance of blood-derived coagulation factors was overlooked for some time in CNS wound healing and scarring. Recent advancements in animal models and human tissue analysis implicate the blood-derived coagulation factor fibrinogen as a molecular link between vascular permeability and scar formation. In this perspective, we summarize the current understanding of how fibrinogen orchestrates scar formation and highlight fibrinogen-induced signaling pathways in diverse neural and non-neural cells that may contribute to scarring in CNS disease. We particularly highlight a role of fibrinogen in the formation of the lesion border between the healthy neural tissue and the fibrotic scar. Finally, we suggest novel therapeutic strategies via manipulating the fibrinogen-scar-forming cell interaction to improve functional outcomes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin hydrochloride (MET)-loaded polycaprolactone (PCL) nanoparticles (NPs) for topical treatment of melanoma. Significance: Topical administration of MET-PCL NPs-CS gel improves penetration of drug, decreases side effects, and increases efficacy of treatment. Methods: MET-PCL NPs were prepared by double emulsion method. Particle size, charge, encapsulation efficiency (EE), release, and morphology were evaluated. MET-PCL NPs-CS gel formulation was characterized in terms of organoleptic properties, pH, gelling time, viscosity, spreadability, release, and morphology. Cytotoxicity was performed on B16F10 cells. Ex vivo permeability was done with pig skin. Results: The size, charge, and EE were found to be 180 ± 10 nm, −11.4 mV, and 93%. SEM images showed that NPs were spherical and smooth. An initial burst release followed by a slower release was observed. MET-PCL NPs-CS gel was found to be transparent. The pH was 4.9 ± 0.05. The gelation time was 1.6 ± 0.2 min. The viscosity results confirm pseudoplastic behavior of gel. The spreadability by % area was 392 ± 6.4 cm. The images showed that gelling network of CS gel was composed of suspended NPs. The viscosity was between 554 and 3503 cP. MET-PCL NPs-CS gel showed prolonged release up to 72 h. On B16F10 cells, gel showed higher cytotoxicity compared to MET solution. MET-PCL NPs-CS gel had twofold higher permeability in pig skin compared with MET-CS gel. Conclusion: Topical administration of MET-PCL NPs-CS gel into the skin resulted in improved dermal penetration and this promising approach may be of value in effective treatment of melanoma and other skin cancers. [ABSTRACT FROM AUTHOR]

Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula. In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells. [ABSTRACT FROM AUTHOR]

AbstractMicroneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles. [ABSTRACT FROM AUTHOR]

Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a "Trojan horse" to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors. [ABSTRACT FROM AUTHOR]

Skin-like soft optical metamaterials with broadband modulation have been long pursued for practical applications, such as cloaking and camouflage. Here, we propose a skin-like metamaterial for dual-band camouflage based on unique Au nanoparticles assembled hollow pillars (NPAHP), which are implemented by the bottom-up template-assisted self-assembly processes. This dual-band camouflage realizes simultaneously high visible absorptivity (~0.947) and low infrared emissivity (~0.074/0.045 for mid-/long-wavelength infrared bands), ideal for visible and infrared dual-band camouflage at night or in outer space. In addition, this self-assembled metamaterial, with a micrometer thickness and periodic through-holes, demonstrates superior skin-like attach-ability and permeability, allowing close attachment to a wide range of surfaces including the human body. Last but not least, benefiting from the extremely low infrared emissivity, the skin-like metamaterial exhibits excellent high-temperature camouflage performance, with radiation temperature reduction from 678 to 353 kelvin. This work provides a new paradigm for skin-like metamaterials with flexible multiband modulation for multiple application scenarios. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)‐overexpressing cutaneous squamous cell carcinoma (CSCC) necessitates more effective therapies due to its elevated metastasis risk compared to the conventional CSCC. While photodynamic therapy (PDT) is a promising way to treat CSCC, effectively administering photosensitizers to reach deeper skin malignancies remains a challenge. Herein, BE‐TEL is reported, a transethosome formulation designed to enhance skin and cutaneous tumor permeability, for targeted treatment of EGFR‐overexpressed CSCC. The formulation is co‐loaded with Erlotinib (Erb), a hydrophobic EGFR inhibitor, and BODIPY (BPY), a photosensitizer. Upon skin penetration and subsequent exposure to 660 nm light, BE‐TEL induces tumor cell apoptosis by reactive oxygen species (ROS) generation and EGFR pathway inhibition. ROS and Erb‐induced metabolic oxidative stress by upregulating the expression of NADPH oxidase 4 (NOX4) can enhance immunogenic cell death (ICD) and promote dendritic cell maturation for tumor‐specific immune response. Furthermore, the EGFR downregulation further mitigated the risk of metastasis and recurrence. In conclusion, BE‐TEL's superior penetration ability together with its combined PDT and EGFR targeted approach paves the way for an efficient strategy against EGFR‐overexpressed CSCC. [ABSTRACT FROM AUTHOR]

Bovine serum albumin (BSA) hydrogels are non-immunogenic, low-cost, biocompatible, and biodegradable. In order to avoid toxic cross-linking agents, gellan was oxidized with NaIO4 to obtain new functional groups like dialdehydes for protein-based hydrogel cross-linking. The formed dialdehyde groups were highlighted with FT-IR and NMR spectroscopy. This paper aims to investigate hydrogel films for biomedical applications obtained by cross-linking BSA with oxidized gellan (OxG) containing immobilized β-cyclodextrin–curcumin inclusion complex (β-CD–Curc) The β-CD–Curc improved the bioavailability and solubility of Curc and was prepared at a molar ratio of 2:1. The film's structure and morphology were evaluated using FT-IR spectroscopy and SEM. The swelling degree (Q%) values of hydrogel films depend on hydrophilicity and pH, with higher values at pH = 7.4. Additionally, the conversion index of -NH2 groups into Schiff bases increases with an increase in OxG amount. The polymeric matrix provides protection for Curc, is non-cytotoxic, and enhances antioxidant activity. At pH = 5.5, the skin permeability and release efficiency of encapsulated curcumin were higher than at pH = 7.4 because of the interaction of free aldehyde and carboxylic groups from hydrogels with amine groups from proteins present in the skin membrane, resulting in a better film adhesion and more efficient curcumin release. [ABSTRACT FROM AUTHOR]

HIV-1 reverse transcriptase (RT) is a crucial enzyme in HIV replication and AIDS progression. It consists of p66 and p51 subunits and converts viral RNA into double-stranded DNA for integration into the host cell's genome. Managing HIV/AIDS depends on inhibiting HIV-1 RT, achieved through nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Understanding RT's structure, catalysis, inhibition, and resistance has been vital for disease management. To study the binding sites and interactions of reverse transcriptase inhibitors (RTIs) with HIV-1 RT, we utilized Molegro Virtual Docker for model preparation and docking. We also employed the SwissADME web tool for predicting physicochemical properties and pharmacokinetics of compounds of interest. We investigated the binding site and affinity of antiretroviral drugs, including delavirdine, tenofovir alafenamide, and atavirdine, with the HIV-1 RT enzyme. Additionally, we evaluated factors such as gastrointestinal absorption, blood-brain barrier penetration, Pgp substrate status, and skin permeability to assess the efficacy of these drugs in treating HIV/AIDS. The findings of this study may help us understand the interactions and potential applications of these compounds with other drugs, ultimately improving antiretroviral therapy for managing HIV-1 infection. Understanding the binding affinity, sites, and pharmacological properties of reverse transcriptase inhibitor compounds is crucial for developing effective antiretroviral therapies against HIV/AIDS. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects. [ABSTRACT FROM AUTHOR]

Objective: Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti‐dandruff commercial products use anti‐fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin. Methods: The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat‐separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted. Results: For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems. Conclusion: To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems. [ABSTRACT FROM AUTHOR]

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems. [ABSTRACT FROM AUTHOR]

The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation. However, combining conventional antibiotics with natural products shows promise in treating SSTIs. The objective of this study is to develop a nanoemulsion-based hydrogel containing Protium spruceanum extract and mupirocin and evaluate its potential for the treatment of SSTIs. The nanoemulsion was obtained by phase inversion and subsequently characterized. The antibacterial activity was evaluated in vitro against S. aureus MRSA, including the synergism of the combination, changes in membrane permeability using flow cytometry, and the anti-biofilm effect. In addition, the irritative potential was evaluated by the HET-CAM assay. The combination exhibited synergistic antibacterial activity against S. aureus and MRSA due to the extract enhancing membrane permeability. The hydrogel demonstrated suitable physicochemical properties, inhibited biofilm formation, and exhibited low irritation. The formulation was nanometric (176.0 ± 1.656 nm) and monodisperse (polydispersity index 0.286 ± 0.011). It exhibited a controlled release profile at 48 h and high encapsulation efficacy (94.29 ± 4.54% for quercitrin and 94.20 ± 5.44% for mupirocin). Therefore, these findings suggest that the hydrogel developed could be a safe and effective option for treating SSTIs. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs), particularly dementia, provide significant problems to worldwide healthcare systems. The development of therapeutic materials for various diseases has a severe challenge in the form of the blood–brain barrier (BBB). Transdermal treatment has recently garnered widespread favor as an alternative method of delivering active chemicals to the brain. This approach has several advantages, including low invasiveness, self-administration, avoidance of first-pass metabolism, preservation of steady plasma concentrations, regulated release, safety, efficacy, and better patient compliance. Topics include the transdermal method for therapeutic NDs, their classification, and the mechanisms that allow the medicine to enter the bloodstream through the skin. The paper also discusses the obstacles and potential outcomes of transdermal therapy, emphasizing the benefits and drawbacks of different approaches. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. Methods: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. Results: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). Conclusion: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]

Pruritus is a common irritating sensation that provokes the desire to scratch. Environmental and genetic factors contribute to the onset of pruritus. Moreover, itch can become a major burden when it becomes chronic. Interestingly, the rare Collagen VI alpha 5 (COL6A5) gene variant p.Glu2272* has been identified in two families and an independent patient with chronic neuropathic itch. These patients showed reduced COL6A5 expression in skin and normal skin morphology. However, little progress has been made until now toward understanding the relationships between this mutation and chronic itch. Therefore, we developed the first mouse model that recapitulates COL6A5-p.Glu2272* mutation using the CRISPR-Cas technology and characterized this new mouse model. The mutant mRNA, measured by RT-ddPCR, was expressed at normal levels in dorsal root ganglia and was decreased in skin. The functional exploration showed effects of the mutation with some sex dysmorphology. Mutant mice had increased skin permeability. Elevated spontaneous scratching and grooming was detected in male and female mutants, with increased anxiety-like behavior in female mutants. These results suggest that the COL6A5-p.Glu2272* mutation found in patients contributes to chronic itch and induces in mice additional behavioral changes. The COL6A5-p.Glu2272* mouse model could elucidate the pathophysiological mechanisms underlying COL6A5 role in itch and help identify potential new therapeutic targets. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis, in short called as RA, is a severe auto-immune condition characterized by thickening of the synovium joints, inflammation and soreness of joints, which subsequently destroys the articular structures. The drug used to treat RA requires the delivery of a formulation in intact form to synovial joints and release of a whole amount of medicine into synovial fluids. Apremilast is an anti-inflammatory drug used to treat arthritis, but its oral drug delivery is limited because of its low bioavailability and side effects. The nanoparticle-based in situ gel helps in prolonged formulation retention, which enables drug release within specific tissues such as cartilage and synovium. The purpose of this research is to formulate and assess the efficacy of a thermosensitive in situ gel of nanosized apremilast for managing RA. A total of nine apremilast- loaded nanoparticles in situ gels designated as F1–F9 were prepared with different ratios of Eudragit RSPO and polyvinyl alcohol using 25% w/v poloxamer 407 and poloxamer 188 as gelling agents. Among the various formulations, F5 showed a particle size of 119 nm, 80.8% EE, 27.54% DL, 37.5 ± 1.7∘C gelation temperature, 55 ± 1.0 second gelation time and 866 ± 13 cps viscosity, with a better in vitro drug release profile of 75.54% for 24 h by non-Fickian diffusion mechanism; thus, it was chosen as the most productive formulation. In an in vivo study in rats, the optimized formulation reduced inflammation at the test site. The developed nanoparticles in situ gel will be a novel carrier system for drugs used to treat RA. [ABSTRACT FROM AUTHOR]

• Glomerular basement membranes are compressible ultrafilters with increased molecular selectivity with increased transmembrane pressure. • Compression effects on glomerular basement membrane sieving are mitigated by crosslinking and stiffening. • Disease-mediated changes in glomerular basement membrane mechanics may contributed to loss of glomerular size selectivity in the setting of chronic kidney disease. Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular permeability of the glomerular filtration barrier combined with saturation or defects in tubular protein reabsorption. Any solute that passes into the glomerular filtrate traverses the glomerular endothelium, the glomerular basement membrane, and the podocyte slit diaphragm. Damage to any layer of the filter has reciprocal effects on other layers to increase glomerular permeability. The GBM is thought to act as a compressible ultrafilter that has increased molecular selectivity with increased pressure due to compression that reduced the porosity of the GBM with increased pressure. In multiple forms of chronic kidney disease, crosslinking enzymes are upregulated and may act to increase GBM stiffness. Here we show that enzymatically crosslinking porcine GBM with transglutaminase increases the stiffness of the GBM and mitigates pressure-dependent reductions in molecular sieving coefficient. This was modeled mathematically using a modified membrane transport model accounting for GBM compression. Changes in the mechanical properties of the GBM may contribute to proteinuria through pressure-dependent effects on GBM porosity. [ABSTRACT FROM AUTHOR]

The skin cancer (mostly of melanoma cells) rate has increased in recent years due to genetic and epigenetic reasons. The efficient treatment of skin cancer is an unmet requirement to achieve specific anticancer activity, reduction of the costs and side effects, and precluding resistance of cancer cells. Hence, employment of proper nanocarriers is promising. Niosomal delivery of loaded drugs or compounds is preffered for skin cancer therapy considering targeted delivery, scalability, biocompatibility, stability and high loading capacity, efficiently killing skin tumor cells. The niosomal formulation of natural and synthetic agents has increased the anticancer and antimicrobial effects on the skin surface. Moreover, niosomal formulation of drugs/compounds have significantly decreased the effective dose or concentration and also mitigated side effects. The stable structure, minimized drug leakage, and efficient delivery to the target tissues can be achieved using niosomal formulation. Future studies will contribute to a deeper understanding and development of more stable nanocarriers, such as combining hybrid niosomes with stabilizing substances such as salts and organic structures for effective drug delivery. [ABSTRACT FROM AUTHOR]

Local species exhibit distinctive indigenous characteristics while showing unique productive and phenotypic traits. However, the advent of commercialization has posed a substantial threat to the survival of indigenous species. Anxi cattle, an endangered native breed in China, have evolved unique growth and reproductive characteristics in extreme desert and semidesert ecosystems. In this study, we conducted a genomic comparison of 10 Anxi cattle genomes with those of five other global populations/breeds to assess genetic diversity and identify candidate genomic regions in Anxi cattle. Population structure and genetic diversity analyses revealed that Anxi cattle are part of the East Asian cattle clade, exhibiting higher genetic diversity than commercial breeds. Through selective sweep analysis, we identified specific genetic variations linked to the environmental adaptability of Anxi cattle. Notably, we identified several candidate genes, including CERS3 involved in regulating skin permeability and antimicrobial functions, RBFOX2 associated with cardiac development, SLC16A7 participated in the regulation of pancreatic endocrine function, and SPATA3 related to reproduction. Our findings revealed the distinctive genomic features of Anxi cattle in dryland environments, provided invaluable insights for further research and breed preservation, and had important significance for enriching the domestic cattle breeding gene bank. [ABSTRACT FROM AUTHOR]

Stem cells are recognized as an important target and tool in regenerative engineering. In this study, we explored the feasibility of engineering amniotic fluid-derived mesenchymal stem cell-secreted molecules (afMSC-SMs) as a versatile bioactive material for skin regenerative medicine applications in a time- and cost-efficient and straightforward manner. afMSC-SMs, obtained in powder form through ethanol precipitation, effectively contributed to preserving the self-renewal capacity and differentiation potential of primary human keratinocytes (pKCs) in a xeno -free environment, offering a potential alternative to traditional culture methods for their long-term in vitro expansion, and allowed them to reconstitute a fully stratified epithelium sheet on human dermal fibroblasts. Furthermore, we demonstrated the flexibility of afMSC-SMs in wound healing and hair regrowth through injectable hydrogel and nanogel-mediated transdermal delivery systems, respectively, expanding the pool of regenerative applications. This cell-free approach may offer several potential advantages, including streamlined manufacturing processes, scalability, controlled formulation, longer shelf lives, and mitigation of risks associated with living cell transplantation. Accordingly, afMSC-SMs could serve as a promising therapeutic toolbox for advancing cell-free regenerative medicine, simplifying their broad applicability in various clinical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: To increase skin permeability, various transdermal delivery techniques have been developed. However, due to the stratum corneum as a skin barrier, transdermal delivery remains limited. Aims: In this study, we evaluated efficacy and safety of arc‐poration as a novel technique disrupting the stratum corneum. Results: Optical images and histological analysis using reconstituted human skin and porcine skin showed that the treatment of arc‐poration created micropores with an average diameter of approximately 100 μm only to the depth of the stratum corneum, but not viable epidermis. In addition, the Franz diffusion cell experiment using reconstituted human skin showed a remarkable increase in permeability following pretreatment with arc‐poration. Clinical results clearly demonstrated the enhancement of the skin‐improving effect of cosmetics by pretreatment of arc‐poration in terms of gloss, hydration, flakiness, texture, tone, tone evenness, and pigmentation of skin, without causing abnormal skin responses. The concentration of ozone and nitrogen oxides generated by arc‐poration was below the permissible value for the human body. Conclusions: Arc‐poration can increase skin permeability by creating stratum corneum‐specific micropores, which can enhance the skin‐improving effect of cosmetics without adverse responses. [ABSTRACT FROM AUTHOR]

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches. [Display omitted] [ABSTRACT FROM AUTHOR]

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others. [ABSTRACT FROM AUTHOR]

Nanocomposite gels consist of nanoparticles dispersed in a gel matrix. The main aim of this work was to develop nanocomposite gels for topical delivery of Flurbiprofen (FB) for humans and farm animals. Nanocomposite gels were prepared stemming from nanoparticles (NPs) freeze-dried with two different cryoprotectants, D-(+)-trehalose (NPs-TRE) and polyethylene glycol 3350 (NPs-PEG), sterilized by gamma (γ) irradiation, and gelled with Sepigel® 305. Nanocomposite gels with FB-NPs-TRE and FB-NPs-PEG were physiochemically characterized in terms of appearance, pH, morphological studies, porosity, swelling, degradation, extensibility, and rheological behavior. The drug release profile and kinetics were assessed, as well as, the ex vivo permeation of FB was assessed in human, porcine and bovine skin. In vivo studies in healthy human volunteers were tested without FB to assess the tolerance of the gels with nanoparticles. Physicochemical studies demonstrated the suitability of the gel formulations. The ex vivo skin permeation capacity of FB-NPs nanocomposite gels with different cryoprotectants allowed us to conclude that these formulations are suitable topical delivery systems for human and veterinary medicine. However, there were statistically significant differences in the permeation of each formulation depending on the skin. Results suggested that FB-NPs-PEG nanocomposite gel was most suitable for human and porcine skin, and the FB-NPs-TRE nanocomposite gel was most suitable for bovine skin. [ABSTRACT FROM AUTHOR]

Repetitive motion or exercise is associated with oxidative stress and muscle inflammation, which can lead to declining grip strength and muscle damage. Oleanolic acid and ursolic acid have anti-inflammatory and antioxidant properties and can be extracted from Chaenomeles speciosa through ultrasonic sonication. We investigated the association between grip strength declines and muscle damage induced by lambda carrageenan (LC) injection and exercise exposure in rats. We also assessed the reparative effects of transdermal pretreatment and post-treatment with C. speciosa extracts (CSEs) by using a supersonic atomizer. The half-maximal inhibitory concentration (IC50) of CSEs for cells was 10.5 mg/mL. CSEs significantly reduced the generation of reactive oxygen species and inflammatory factors (interleukin [IL]-6 and IL-1β) in in vitro cell tests. Rats subjected to LC injection and 6 weeks of exercise exhibited significantly increased inflammatory cytokine levels (IL-1β, TNF-α, and IL-6). Hematoxylin and eosin staining revealed inflammatory cell infiltration and evident muscle damage in the gastrocnemius muscle, which exhibited splitting and the appearance of the endomysium and perimysium. The treated rats' grip strength significantly declined. Following treatment with CSEs, the damaged muscles exhibited decreased IL-1β, TNF-α, and IL-6 levels and normal morphologies. Moreover, grip strength significantly recovered. Pretreatment with CSEs yielded an immediate and significant increase in grip strength, with an increase of 180% and 165% occurring in the rats exposed to LC injection and exercise within the initial 12 h period, respectively, compared with the control group. Pretreatment with CSEs delivered transdermally using a supersonic atomizer may have applications in sports medicine and training or competitions. [ABSTRACT FROM AUTHOR]

Triboelectric nanogenerators (TENGs) have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices. Despite their potential benefits, the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy. Therefore, further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications. In this study, we present a flexible silk fibroin-based triboelectric nanogenerator (SFB-TENG) that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability. The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926, NIH-3T3 and RSC96 cells. However, apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz. In addition, the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells. This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design, as well as its safe operating conditions for use in biomedical applications. These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration. [ABSTRACT FROM AUTHOR]