Search

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., (© 2024 American Society for Photobiology.)

Background: Machine learning algorithms that can quickly and easily estimate skin permeability (Kp) are increasingly being used in drug delivery research. The linear free energy relationship (LFER) developed by Abraham is a practical technique for predicting Kp. The permeability coefficients and Abraham solute descriptor values for 175 organic compounds have been documented in the scientific literature. Purpose: The purpose of this project was to use a publicly available dataset to make skin permeability predictions using the random forest and XBoost regression techniques. Methods: We employed Pandas-based methods in JupyterLab to predict permeability coefficient (Kp) from solute descriptors (excess molar refraction [E], combined dipolarity/polarizability [S], overall solute hydrogen bond acidity and basicity [A and B], and the McGowan's characteristic molecular volume [V]). Results: The random forest and XG Boost regression models established statistically significant association between the descriptors and the skin permeability coefficient.

Improving the permeability and solubility of poorly water-soluble compounds is a major difficulty in skin permeation. In this study, we investigated whether using a pharmaceutical technique such as applying coamorphous to a microemulsion enhances the skin permeation of polyphenolic compounds. The melt-quenching technique created the coamorphous system between naringenin (NRG) and hesperetin (HPT), two polyphenolic compounds with poor water solubility. By creating a supersaturated state, the aqueous solution of coamorphous NRG/HPT demonstrated improved NRG and HPT skin permeation. However, as both compounds precipitated, the supersaturation ratio decreased. In contrast to crystal compounds, incorporating coamorphous material into microemulsions enabled the preparation of microemulsions in a wider formulation range. Additionally, compared to microemulsions with crystal compounds and an aqueous suspension of coamorphous, microemulsions with coamorphous NRG/HPT increased skin permeation of both compounds by more than four times. These results suggested that interactions between NRG and HPT are maintained in the microemulsion and enhance both compounds' skin permeation. An approach for improving the skin permeation of poorly water-soluble chemicals would be to apply a coamorphous system to a microemulsion., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: The skin offers various benefits and potential for peptide delivery if its barrier performance can be reduced temporarily and reversibly. As peptides possess high molecular weight, hydrophilic nature (in most cases), and ionizable groups in the structure, their skin delivery is highly challenging. Apart from this, they are susceptible to the proteolytic enzymes in the skin. Anti-wrinkle peptides, like other peptides, suffer from insufficient skin permeability, while most of them must penetrate deep in the skin to present their efficacy. Although the cellular studies indicate the effectiveness of such peptides, without the ability to permeate the skin sufficiently, this efficacy is useless. Poor skin permeability of anti-wrinkle peptides has led to ongoing research for finding feasible and noninvasive enhancement methods that would be desirable for consumers of cosmetic products., Method: In this paper, the possibility of skin permeation of anti-wrinkle peptides as well as the chemical, physical, and encapsulation approaches that have been employed to date to increase permeability of these difficult molecules are thoroughly reviewed., Results: Most anti-wrinkle peptides are not appropriate candidates for skin permeation and the use of enhancement methods is essential to increase their permeability. To do so, only some permeability enhancement approaches have been applied so far, including chemical modification with hydrophobic moieties or cell penetrating peptides, metal complexation, chemical permeation enhancers, iontophoresis, microneedles, and encapsulation in nanocarriers. The results of studies published on the skin permeability of anti-wrinkle peptides carnosine, GHK, PKEK, GEKG, GQPR, and KTTKS indicate that the skin permeability of these peptides can be successfully increased., Conclusion: Although the skin permeability of most anti-wrinkle peptides is not high enough and most anti-wrinkle peptides might not reach their targets in the skin at right concentrations, their permeability can be increased to therapeutic concentrations using various enhancement approaches., (© 2022 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated ( 6c ) and chlorinated ( 6g ) indole moieties led to enhanced anti-hyaluronidase activity (IC 50 = 80.3 vs. 9.97 and 9.57 µg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH = 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with anti-hyaluronidase activity.

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1-10%), salicylic acid (0.2-2%), and lactobionic acid (1.2-12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50-80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

In vitro assessment of topical (dermal) pharmacokinetics is a critical aspect of the drug development process for semi-solid products (e.g., solutions, foams, sprays, creams, gels, lotions, ointments), allowing for informed selection of new chemical entities, optimization of prototype formulations during the nonclinical stage, and determination of bioequivalence of generics. It can also serve as a tool to further understand the impact of different excipients on drug delivery, product quality, and formulation microstructure when used in parallel with other techniques, such as analyses of rheology, viscosity, microscopic characteristics, release rate, particle size, and oil droplet size distribution. The in vitro permeation test (IVPT), also known as in vitro skin penetration/permeation test, typically uses ex vivo human skin in conjunction with diffusion cells, such as Franz (or vertical) or Bronaugh (or flow-through) diffusion cells, and is the technique of choice for dermal pharmacokinetics assessment. Successful execution of the IVPT also involves the development and use of fit-for-purpose bioanalytical methods and procedures. The protocols described herein provide detailed steps for execution of the IVPT utilizing flow-through diffusion cells and for key aspects of the development of a liquid chromatography-tandem mass spectrometry method intended for analysis of the generated samples (epidermis, dermis, and receptor solution). © 2020 Wiley Periodicals LLC. Basic Protocol 1: In vitro permeation test Support Protocol: Dermatoming of ex vivo human skin Basic Protocol 2: Bioanalytical methodology in the context of the in vitro permeation test., (© 2020 Wiley Periodicals LLC.)

This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility. In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of present study was to develop a rotigotine (ROT) transdermal patch by converting ROT to a form of deep eutectic 'liquid co-crystal'. Formulation factors including the type of ROT-organic acid deep eutectics, pressure sensitive adhesives (PSAs), drug-loading and patch thickness were investigated by in vitro skin permeation study and the optimized patch was evaluated by pharmacokinetics study. It was particularly concerned about the drug-polymer miscibility and skin permeability of ROT-lactic acid deep eutectics (ROT-LA). FTIR study, thermal analysis and molecular modeling were conducted to investigate the drug-PSA interaction. Multiple linear regression was performed to investigate the mechanism of the promoted skin permeability. The results showed that strong interaction was observed between ROT-LA and hydroxyl PSA, which inhibited the formation of ROT crystals. Skin permeability of ROT-organic acids deep eutectics were improved by the variations of apparent partition coefficient and glass transition temperature. AUC 0-t and C max of optimized patch were 1290.6 ± 102.7 h ng/mL and 60.7 ± 12.0 ng/mL, respectively, which had no significant difference with commercial product. In conclusion, a reduced administration area (75%) and low risk of crystallization were introduced by the ROT deep eutectics, which demonstrated the feasibility of improving drug-polymer miscibility and skin permeability of transdermal drug., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Transdermal drug delivery has many advantages compared to other routes. However, the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum and it was found that applying different ultrasound waves could enhance the skin's permeability., Objective: The aim of this work is to study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation., Method: The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method., Results: The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was also found upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane., Conclusion: Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Exposure of the skin to low-frequency ultrasound in the Franz diffusion cell has been found to increase the permeability of the skin to molecular transport. In many cases, significant heating of the coupling fluid requires the use of duty cycles that extend the total experimental time. This is a methodological study in which the coupling fluid is circulated between a modified Franz diffusion cell and a heat exchanger to allow for the continuous application of low-frequency ultrasound while the coupling fluid temperature is held constant. Dermatomed porcine skin was exposed to continuous ultrasound at 20 kHz for 10 min at an intensity of 55 W/cm 2 while the coupling fluid was maintained at one of three target temperatures (13°C, 33°C or 46°C). Foil pitting and passive cavitation detection revealed that inertial cavitation activity decreased with increasing coupling fluid target temperature. Transport measurements revealed an increase in mean donor calcein concentration with increasing coupling fluid temperature, though these were not statistically significant. Taken together these findings suggest that the weakened stratum corneum lipid structure at higher temperatures is more susceptible to the introduction of defects from the jetting of cavitation., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Onychomycosis is a progressive fungal infection of the nails that involves the deeper nail layer and nail bed. It is important to maintain sufficient drug concentration in the diseased tissues after topical application. In this study, a stable topical delivery system for efinaconazole (EFN) was designed to enhance absorption potential through the skin and nail plate by incorporating ethanol, diethylene glycol monoethyl ether (Transcutol P) and isopropyl myristate, and cyclomethicone into the topical solution as a delivery vehicle, permeation enhancers, and a wetting agent, respectively. In addition, the stability of EFN in the formulation was significantly improved by adding butylated hydroxytoluene, diethylenetriamine pentaacetic acid, and citric acid as an antioxidant, chelating agent, and pH-adjusting agent, respectively, without discoloration. The optimum EFN formulation (EFN-K) showed 1.46-fold greater human skin permeation than that of the reference control (commercial 10% EFN topical solution). Furthermore, after a 24-hour incubation, the amount of infiltrated EFN from EFN-K in the human nail plate was 4.11-fold greater than that of the reference control, resulting in an 89.7% increase in nail flux at 7 days after treatment. EFN-K significantly accelerated structural recovery of the keratin layer in a Trichophyton mentagrophytes -infected guinea pig onychomycosis model, decreasing the mean viable fungal cell count by 54.3% compared to the vehicle-treated group after once-daily treatment for 4 weeks. Thus, the accelerated skin and nail penetration effect of EFN-K is expected to achieve good patient compliance, and improve the complete cure rate of onychomycosis.

The control of permeation is vital not only for the topical application of lotions, creams, and ointments but also for the toxicological and risk assessment of materials from environmental and occupational hazards. To understand the effects of physicochemical properties of a variety of 211 compounds on skin permeability, we developed a three-dimensional quantitative structure-property relationship (3 D-QSPR) model. Alignment free GRid-INdependent Descriptors (GRINDs), which were derived from molecular interaction fields (MIFs) contributed to the regression models. Kennard-Stone algorithm was employed to split data set to a training set of 159 molecules and a test set of 52 molecules. Fractional factorial design (FFD), genetic algorithm (GA) and successive projection algorithm (SPA) were applied to select the most relevant 3 D molecular descriptors. The descriptors selected using various feature selection were correlated with skin permeability constants by partial least squares (PLS) and support vector machine (SVM). SPA-SVM model gave prominent statistical values with the correlation coefficient of [Formula: see text]= 0.96, Q 2 = 0.73 and R 2 =0.76. According to the analysis results, the hydrogen bonding donor and acceptor properties of the investigated compounds can influence the penetration into the human skin. Furthermore, it was found that permeability was enhanced by increasing the hydrophobicity and was diminished by increasing the molecular weight. In addition, the presence of hydrophobic groups in the target molecule, as well as their shape and position, can affect the skin permeability.pred =0.76. According to the analysis results, the hydrogen bonding donor and acceptor properties of the investigated compounds can influence the penetration into the human skin. Furthermore, it was found that permeability was enhanced by increasing the hydrophobicity and was diminished by increasing the molecular weight. In addition, the presence of hydrophobic groups in the target molecule, as well as their shape and position, can affect the skin permeability.

The skin is the main barrier between the internal body environment and the external one. The characteristics of this barrier and its properties are able to modify and affect drug delivery and chemical toxicity parameters. Therefore, it is not surprising that permeability of many different compounds has been measured through several in vitro and in vivo techniques. Moreover, many different in silico approaches have been used to identify the correlation between the structure of the permeants and their permeability, to reproduce the skin behavior, and to predict the ability of specific chemicals to permeate this barrier. A significant number of issues, like interlaboratory variability, experimental conditions, data set building rationales, and skin site of origin and hydration, still prevent us from obtaining a definitive predictive skin permeability model. This review wants to show the main advances and the principal approaches in computational methods used to predict this property, to enlighten the main issues that have arisen, and to address the challenges to develop in future research.

Anionic surfactants are often used for cleaning and pharmaceutical purposes because of their strong surfactancy and foaming property. However, they are rarely ingested orally, the skin is a part of the human body most affected by surfactants. Barrier function of the skin is very strong, but the anionic surfactants can cause serious damages to it. Recently, amino acid-based surfactants have attracted attention as a safer option owing to their biocompatibility. Cytotoxicity examinations revealed that the amino acid-based surfactants are superior to sulfate-based surfactants. However, a systematical and comprehensive study related to the effect of these surfactants on skin barrier function has not yet been reported. In this work, skin permeation test using the skin of hairless mice and HPLC method is carried out. The material transmission speed through skin in a steady state was different between each surfactant treatment. We performed a comprehensive analysis of the effect of surfactants on skin barrier function and defined Transmission Index as an index for the degree of effect of surfactants. Glutamate series amino acid-based surfactant were effective to Transmission Index and we guessed the cause was due to adsorption. Based on the finding this study, we suggest using adsorptive property as a measure to the effect on the skin barrier function.

The poultice formulation is a patch containing a large amount of water. It is known that the water contained in the adhesive polymer layer (ADPL) of poultice affects the cooling sensation and skin permeability of the active pharmaceutical ingredient (API). In this study, we evaluated the relationship between the water content in a ketoprofen poultice formulation and the amount of time the poultice was left out at room temperature after removal from the airtight container, as well as the influence of the decreasing water content on the skin permeability of the API. After removing the poultice from the container for 1 h, the mass of the ADPL decreased by approximately 40%. When the near-infrared (NIR) spectrum of the ADPL of poultice was measured, the peaks reflecting the hydroxyl group were attenuated depending on the time left out at room temperature. It is suggested that the changes in the mass and NIR spectrum of the ADPL are caused by the change in the water content. Moreover, when the permeability of API was evaluated on hairless mouse skin, the cumulative skin permeation amount and flux decreased, while the lag time was prolonged as the time left out increased. These results suggest that the skin permeability of the API is impaired by water evaporation and that maintaining the water in the ADPL in poultice is very important from not only the viewpoint of cooling sensation, tackiness and moisturizing but also the skin permeability of the API.

Claw diseases like interdigital dermatitis and footrot threaten sheep health and are major welfare issues. Several studies mainly done in cattle suggested that zinc (Zn) supplementation may improve claw integrity. However, Zn supplements may differ markedly regarding Zn bioavailability. Zn bound to single amino acids has been shown to be more bioavailable than inorganic Zn sources. The aim of this study was to determine the effect of different Zn supplements on the integrity of the claw and interdigital skin of healthy sheep. At weaning 30 Merino lambs were randomly allocated to three different dietary treatments which were provided through the pelleted concentrates as follows: 1) no supplemental Zn (Zn0); 2) addition of 40 mg/kg Zn as Zn sulphate (ZnS); 3) addition of 40 mg/kg organic Zn as Zn amino acid complex (CZn). Barley straw and pelleted concentrates were given ad-libitum. The calculated Zn concentration of the total diet (roughage and concentrate) without supplemental Zn (Zn0) was 38 mg Zn/kg DM. The concentrates were formulated to meet the nutritional requirements for growing lambs and contained 207 g/kg DM crude protein and 12.4 MJ/kg DM metabolizable energy. After 8 weeks the lambs were slaughtered and the following specimens were collected: blood serum, liver, sole and coronary band of the claw, and interdigital skin. Serum and tissue Zn and copper (Cu) concentrations and claw hardness were determined. Routine pathohistology and electron microscopy were conducted. Franz diffusion cell system and Ki-67 immunostaining were used to determine the permeability of the interdigital skin and the keratinocyte proliferation in the basal layer of sole horn, coronary band and interdigital skin, respectively. The concentrations of Zn and Cu in serum and liver tissue as well as the Zn concentration in claw horn were not affected by dietary treatment. Zn0 lambs showed higher (p < 0.05) Cu concentrations in claw horn compared to both Zn supplemented groups. Routine pathohistology as well as electron microscopy did not show significant morphological differences between the three groups. Franz diffusion cell system proved to be a suitable method examining the interdigital skin permeability, but the group differences in this study were not significant. Dietary treatment did not affect keratinocyte proliferation in the coronary band. In the sole keratinocyte proliferation was significantly higher (p < 0.05) in the Zn0 group compared to CZn with ZnS being intermediate. Keratinocyte proliferation in the interdigital skin was significantly higher (p < 0.05) in the CZn group compared to the Zn0 with ZnS being intermediate. The results of the current experiment indicate that serum and tissue Zn concentrations and horn hardness are not affected by adding a moderate amount of Zn sulphate or Zn amino acid complex to a basal diet. However, supplemental Zn amino acid complex seems to affect keratinocyte proliferation of interdigital skin and sole horn of lambs. Effects on skin permeability should be retested using a higher number of animals prospectively., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Ceramides (CERs) are the backbone of the intercellular lipid lamellae of the stratum corneum (SC), the outer layer of the skin. Skin diseases such as atopic dermatitis, psoriasis, and aged skin are characterized by dysfunctional skin barrier and dryness which are associated with reduced levels of CERs. Replenishing the depleted epidermal CERs with exogenous CERs has been shown to have beneficial effects in improving the skin barrier and hydration. The exogenous CERs such as phyto-derived CERs (PhytoCERs) can be delivered deep into the SC using novel topical formulations. This, however, requires investigating the rate and extent of skin permeation of CERs. In this study, an LC/APCI-MS method to detect and quantify PhytoCERs in different layers of the skin has been developed and validated. The method was used to investigate the skin permeation of PhytoCERs using Franz diffusion cells after applying an amphiphilic cream containing PhytoCERs to the surface of ex vivo human skin. As plant-specific CERs are not commercially available, well-characterized CERs isolated from oat (Avena abyssinica) were used as reference standards for the development and validation of the method. The method was linear over the range of 30-1050 ng/mL and sensitive with limit of detection and quantification of 10 and 30 ng/mL, respectively. The method was also selective, accurate, and precise with minimal matrix effect (with mean matrix factor around 100%). Even if more than 85% of oat CERs in the cream remained in the cream after the incubation periods of 30, 100, and 300 min, it was possible to quantify the small quantities of oat CERs distributed across the SC, epidermis, and dermis of the skin indicating the method's sensitivity. Therefore, the method can be used to investigate the skin permeation of oat CERs from the various pharmaceutical and cosmeceutical products without any interference from the skin constituents such as the epidermal lipids. Graphical abstract ᅟ.

Deficiency or altered composition of stratum corneum (SC) lipids such as ceramides (CERs), causing skin barrier dysfunction and skin dryness, have been associated with skin diseases such as atopic dermatitis and psoriasis, and ageing. Replenishing the depleted native CERs with exogenous CERs has also been shown to have beneficial effects in restoring the skin barrier. Phyto-derived CERs such as oat CERs were shown to be potential for skin barrier reinforcement. To effect this, however, the oat CERs should overcome the SC barrier and delivered deep into the lipid matrix using the various novel formulations. In an attempt to demonstrate the potential use of oat CERs, lecithin-based microemulsions (MEs) and starch-based nanoparticles (NPs) were formulated and characterized. Besides, ME gel and NP gel were also prepared using Carbopol®980 as a gelling agent. The in vitro release and penetration (using artificial four-layer membrane system) and ex vivo permeation (using excised human skin) of oat CERs from the various formulations were investigated. The results revealed ME enhanced the in vitro release and penetration oat CERs compared to the other formulations. On the other hand, the NPs retarded the release of oat CERs and small quantities of oat CERs incorporated into NP gel penetrated into the deeper layers of the multilayer membranes. The penetration-enhancing effect of ME was also observed in the ex vivo permeation studies where significant quantities of oat CERs were found in the acceptor compartment. Compared to the ME, the ME gel exhibited reduced depth and extent of oat CERs permeation. As compared to NP gel, ME gel enhanced the degree of permeation of oat CERs into the deeper layer of the skin. Generally the gel formulations were effective in concentrating oat CERs in the SC where they are needed to be., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The skin permeability ( Kp ) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical's skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Due to advances in telemedicine, mobile medical care, wearable health monitoring, and electronic skin, great efforts have been directed to non-invasive monitoring and treatment of disease. These processes generally involve disease detection from interstitial fluid (ISF) instead of blood, and transdermal drug delivery. However, the quantitative extraction of ISF and the level of drug absorption are greatly affected by the individual's skin permeability, which is closely related to the properties of the stratum corneum (SC). Therefore, measurement of SC impedance has been proposed as an appropriate way for assessing individual skin differences. In order to figure out the current status and research direction of human SC impedance detection, investigations regarding skin impedance measurement have been reviewed in this paper. Future directions are concluded after a review of impedance models, electrodes, measurement methods and systems, and their applications in treatment. It is believed that a well-matched skin impedance model and measurement method will be established for clinical and point-of care applications in the near future., Competing Interests: The authors declare no conflict of interest.

Experimental values of permeability coefficients, as log K p , of chemical compounds across human skin were collected by carefully screening the literature, and adjusted to 37°C for the effect of temperature. The values of log K p for partially ionized acids and bases were separated into those for their neutral and ionic species, forming a total data set of 247 compounds and species (including 35 ionic species). The obtained log K p values have been regressed against Abraham solute descriptors to yield a correlation equation with R 2 =0.866 and SD=0.432 log units. The equation can provide valid predictions for log K p of neutral molecules, ions and ionic species, with predictive R 2 =0.858 and predictive SD=0.445 log units calculated by the leave-one-out statistics. The predicted log K p values for Na + and Et 4 N + are in good agreement with the observed values. We calculated the values of log K p of ketoprofen as a function of the pH of the donor solution, and found that log K p markedly varies only when ketoprofen is largely ionized. This explains why models that neglect ionization of permeants still yield reasonable statistical results. The effect of skin thickness on log K p was investigated by inclusion of two indicator variables, one for intermediate thickness skin and one for full thickness skin, into the above equation. The newly obtained equations were found to be statistically very close to the above equation. Therefore, the thickness of human skin used makes little difference to the experimental values of log K p ., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fingolimod (FNGL) is an immune-modulatory agent prescribed for relapsing forms of multiple sclerosis. Because of its mechanism of action, FNGL is potentially a treatment for chronic, non-curable T-lymphocyte-driven inflammatory skin diseases (TLDISD) such as psoriasis and atopic dermatitis. Since severe side effects limit the systemic administration of FNGL, the objective of this study is to develop a hydroxypropyl cellulose (2%) FNGL gel for dermatological applications. First, the effect of FNGL strength (0.05%, 0.10%, 0.50%, and 1.00%) on skin permeability and retention was investigated. We carried out several permeation studies with vertical Franz diffusion cells and (i) cellulose or (ii) excised dorsal porcine ear skin (EDPES) as membrane. We also quantified FNGL in the stratum corneum and in dermis with the tape-stripping method. Permeability parameters as well as the amount retained in skin increased significantly (p < 0.01) with strength; however, there was no statistically significant difference between the 0.50% and 1.00% gels for both cellulose and EDPES. Therefore, we selected the 0.50% gel to investigate the effect of colloidal oatmeal (0%, 1%, 3%, 6%, and 10%) on FNGL in vitro permeability and skin retention. Colloidal oatmeal has beneficial dermatological properties for TLDISD and may complement FNGL activity. Permeability increased significantly (p < 0.001) with colloidal oatmeal at the 6% and 10% strength with an enhancement ratio of 3.5 and 2.4, respectively, whereas the amount retained in the skin decreased significantly (p < 0.001) compared to the base gel. In conclusion, the 0.50% FNGL(.)HCL gel with 6% Aveeno® has very promising permeability characteristics for delivery of FNGL to the skin.

Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac alone patch, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine alone patch. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The effect of vehicle mixtures on transdermal permeation has been studied using transient flux profiles from porcine skin flow through diffusion cells. Such data characteristically exhibit a large amount of variability between treatments (vehicle and penetrant combinations) as well as noise within treatments. A novel mathematical model has been used that describes longitudinal variation as a time varying diffusivity. Between treatment variability was described by a mixed effects model. A quantitative structure property relationship (QSPR) was developed to describe the effects of the penetrant and vehicle mixture properties on the mean diffusivity and partition coefficient in the membrane. The relationship included terms for the logP and molecular weight of the penetrant and the refractive index of the vehicle mixture with R(2)>0.95 for K and >0.9 for partition coefficient (as K⋅D). This analysis improved on previous work, finding a more parsimonious model with higher predictability, while still identifying the mixture refractive index as a key descriptor in predicting vehicle effects. The concordance with established and expected relationships lends confidence to this new methodology for evaluating transient, finite dose, transdermal flux data collected using traditional experimental methods., (Copyright © 2015. Published by Elsevier B.V.)

Purpose: The solvent effect on skin permeability is important for assessing the effectiveness and toxicological risk of new dermatological formulations in pharmaceuticals and cosmetics development. The solvent effect occurs by diverse mechanisms, which could be elucidated by efficient and reliable prediction models. However, such prediction models have been hampered by the small variety of permeants and mixture components archived in databases and by low predictive performance. Here, we propose a solution to both problems., Methods: We first compiled a novel large database of 412 samples from 261 structurally diverse permeants and 31 solvents reported in the literature. The data were carefully screened to ensure their collection under consistent experimental conditions. To construct a high-performance predictive model, we then applied support vector regression (SVR) and random forest (RF) with greedy stepwise descriptor selection to our database. The models were internally and externally validated., Results: The SVR achieved higher performance statistics than RF. The (externally validated) determination coefficient, root mean square error, and mean absolute error of SVR were 0.899, 0.351, and 0.268, respectively. Moreover, because all descriptors are fully computational, our method can predict as-yet unsynthesized compounds., Conclusion: Our high-performance prediction model offers an attractive alternative to permeability experiments for pharmaceutical and cosmetic candidate screening and optimizing skin-permeable topical formulations.

Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R(2)=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q(2)ext=0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Penetrable silica possesses hierarchical pores, mesopores and penetrable macropores, offering fast mass transfer, satisfactory mechanical strength as well as low column pressure. In the present study, penetrable octadecyl-bonded silica (ODS) was for the first time used as biopartitioning micellar chromatography (BMC) stationary phase to profile ecotoxicity and skin permeability of benzophenone UV-filters. Mobile phase (MP) pH and concentration of polyoxyethylene(23)lauryl ether in the MP were systematically studied. Quantitative retention-activity relationships (QRARs) model was established to correlate retention factors (k) on BMC with bioconcentration factor (BCF) and transdermal rate (TR) of UV-filters. Coefficient of determination (r(2)) of the QRARs model between log BCF and log k were 0.9398-0.9753, while r(2) between TR and log k were 0.7569-0.8434, which demonstrated satisfactory predictive ability of the methodology. It was a powerful tool for fast screening by combining penetrable ODS with BMC, and avoiding column blockage often occurring in BMC., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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]

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]

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: 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]

The HUMIMIC skin‐liver Chip2 microphysiological systems model using the epidermal model, EpiDerm™, was reported previously to mimic application route‐dependent metabolism of the hair dye, 4‐amino‐2‐hydroxytoluene (AHT). Therefore, we evaluated the use of alternative skin models—SkinEthic™, EpiDermFT™ and PhenionFT™—for the same purpose. In static incubations, AHT permeation was similar using SkinEthic™ and EpiDerm™ models. Older Day 21 (D21) SkinEthic™ models with a thicker stratum corneum did not exhibit a greater barrier to AHT (overall permeation was the same in D17 and D21 models). All epidermal models metabolised AHT, with the EpiDerm™ exhibiting higher N‐acetylation than SkinEthic™ models. AHT metabolism by D21 SkinEthic™ models was lower than that by D17 SkinEthic™ and EpiDerm™ models, thus a thicker stratum corneum was associated with fewer viable cells and a lower metabolic activity. AHT permeation was much slower using PhenionFT™ compared to epidermal models and better reflected permeation of AHT through native human skin. This model also extensively metabolised AHT to N‐acetyl‐AHT. After a single topical or systemic application of AHT to Chip2 model with PhenionFT™, medium was analysed for parent and metabolites over 5 days. The first‐pass metabolism of AHT was demonstrated, and the introduction of a wash step after 30 min decreased the exposure to AHT and its metabolites by 33% and 40%–43%, respectively. In conclusion, epidermal and FT skin models used in the Chip2 can mimic the first‐pass skin metabolism of AHT. This highlights the flexibility of the Chip2 to incorporate different skin models according to the purpose. We evaluated the use of SkinEthic™, EpiDermFT™ and PhenionFT™ in the HUMIMIC skin‐liver Chip2 microfluidic model to mimic the application‐dependent metabolic fate of 4‐amino‐2‐hydroxytoluene (AHT). In static incubations, all models metabolised AHT to N‐acetyl‐AHT and permeation across PhenionFT™ was much slower than across epidermal models. In the Chip2 using PhenionFT™, first‐pass metabolism of AHT was demonstrated and washing the skin after 30 min decreased exposure to AHT equivalents. This highlights the flexibility of the Chip2 to incorporate different skin models. [ABSTRACT FROM AUTHOR]

Background: Canine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD. Objective: To this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed. Results: Since the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD. Conclusion and Clinical Relevance: Although many studies have been published since 2015, the understanding of the cutaneous host–microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome. [ABSTRACT FROM AUTHOR]

In Vitro Permeation Test (IVPT) is commonly used to evaluate skin penetration of chemicals and performance of dermatological products. For a permeant with low aqueous solubility, an additive that is expected not to alter the skin barrier can be used in the receptor solution to improve permeant solubility. The objective of this study was to (a) evaluate the effects of these additives in IVPT receptor solution on skin permeability of model permeants and skin electrical resistance and (b) determine the solubility of the permeants in these receptor solutions. Bovine serum albumin (BSA), 2-hydroxypropyl-beta-cyclodextrin (HPCD), ethanol, nonionic surfactant Brij-98, and propylene glycol were the additives, and phosphate buffered saline (PBS) was the control. Steady-state skin permeability coefficients and resistances were determined. The receptor solutions examined in this study did not cause a significant increase in skin permeability or decrease in resistance (less than 40 % changes) except 25 % ethanol. The receptor solution containing 25 % ethanol induced an approximately twofold average increase in skin permeability and reduced skin electrical resistance by approximately threefold. The receptor solution of 2.5 % HPCD provided the highest levels of solubility for the model lipophilic permeants, while 0.2 % Brij-98 and 5 % ethanol showed the lowest solubility enhancement from those in PBS. [ABSTRACT FROM AUTHOR]

Skin plays crucial roles in the human body: besides protecting the organism from external threats, it acts as a thermal regulator, is responsible for the sense of touch, hosts microbial communities (the skin microbiota) involved in preventing the invasion of foreign pathogens, contains immunocompetent cells that maintain a healthy immunogenic/tolerogenic balance, and is a suitable route for drug administration. In the skin, four defense levels can be identified: besides the physical, chemical, and immune barriers that are inherent to the tissue, the skin microbiota (i.e., the numerous microorganisms living on the skin surface) provides an additional barrier. Studying the skin barrier function or the effects of drugs or cosmetic agents on human skin is a difficult task since snapshot evidence can only be obtained using bioptic samples where dynamic processes cannot properly be followed. To overcome these limitations, many different in vitro models of human skin have been developed that are characterized by diverse levels of complexity in terms of chemical, structural, and cellular composition. The aim of this review is to summarize and discuss the advantages and disadvantages of the different human skin models so far available and to underline how the insertion of a proper microbiota would positively impact an in vitro human skin model in an attempt to better mimic conditions in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Acne vulgaris can be treated topically with adapalene, a synthetic derivative of naphthoic acid with retinoid activity. Adapalene has a very low rate of percutaneous absorption and is almost completely insoluble in water. To obviate this problem, microemulsion (ME) carrier is used. The study's goals were to create and characterize adapalene‐loaded ME and assess the drug's transfollicular route of penetration to see if hair follicles can serve as a conduit for the drug to enter the skin. Methods: Adapalene microemulsions (MEs) are made by combining the right amounts of the cosurfactant (propylene glycol), surfactant (Tween 80 and Span 20), and oil phase (oleic acid–Transcutol P (10:1)). Physical and chemical characteristics of MEs, including droplet size, stability, viscosity, drug release, and in vitro skin permeability via guinea pigs' hairy and non‐hairy skin, were assessed. Results: The range of 13.86–56.16 nm was found to be the average droplet size of ME formulations. The range of viscosities was 117–240 cps. The drug release profile reveals that 95.374 percent of the drug was released within the experiment's first 24 h. Compared to the adapalene control (aqueous suspension), all MEs enhanced the adapalene flow through both hairy and non‐hairy skin. The surfactant/cosurfactant ratio had an impact on the amount of drug that passed through both skins because a larger ratio enhanced the adapalene affinity in the follicular route. Conclusion: Furthermore, the proportions of the water and oil phases in formulations, as well as the S/C ratio, have a significant impact on the physicochemical characteristics and adapalene permeability across both pathways. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic (PBPK) models of skin absorption are a powerful resource for estimating drug delivery and chemical risk of dermatological products. This paper presents a PBPK workflow for the quantification of the mechanistic determinants of skin permeability and the use of these quantities in the prediction of skin absorption in novel contexts. A state-of-the-art mechanistic model of dermal absorption was programmed into an open-source modeling framework. A sensitivity analysis was performed to identify the uncertain compound-specific, individual-specific, and site-specific model parameters that impact permeability. A Bayesian Markov Chain Monte Carlo algorithm was employed to derive distributions of these parameters given in vitro experimental permeability measurements. Extrapolations to novel contexts were generated by simulating the model following its update with samples drawn from the learned distributions as well as parameters that represent the intended scenario. This algorithm was applied multiple times, each using a unique set of permeability measurements sourced under experimental contexts that differ in terms of the compound, vehicle pH, skin sample anatomical site, and the number of compounds under which each subject's skin samples were tested. Among the data sets used in this study, the highest accuracy and precision in the extrapolated permeability was achieved in those that include measurements conducted under multiple vehicle pH levels and in which individual subjects' skin samples are tested under multiple compounds. This work thus identifies factors for consideration in the design of experiments for the purpose of training dermal models to robustly estimate drug delivery and chemical risk. [ABSTRACT FROM AUTHOR]

Triclosan is an anti-microbial chemical incorporated into products that are applied to the skin of healthcare workers. Exposure to triclosan has previously been shown to be associated with allergic disease in humans and impact the immune responses in animal models. Additionally, studies have shown that exposure to triclosan dermally activates the NLRP3 inflammasome and disrupts the skin barrier integrity in mice. The skin is the largest organ of the body and plays an important role as a physical barrier and regulator of the immune system. Alterations in the barrier and immune regulatory functions of the skin have been demonstrated to increase the risk of sensitization and development of allergic disease. In this study, the impact of triclosan exposure on the skin barrier and keratinocyte function was investigated using a model of reconstructed human epidermis. The apical surface of reconstructed human epidermis was exposed to triclosan (0.05-0.2%) once for 6, 24, or 48 h or daily for 5 consecutive days. Exposure to triclosan increased epidermal permeability and altered the expression of genes involved in formation of the skin barrier. Additionally, exposure to triclosan altered the expression patterns of several cytokines and growth factors. Together, these results suggest that exposure to triclosan impacts skin barrier integrity and function of human keratinocytes and suggests that these alterations may impact immune regulation. [ABSTRACT FROM AUTHOR]

Oxygen is required for cell migration into the scaffold and for the survival of the overlying graft in the use of a single-layer scaffold. In the absence of diffusion from the avascular wound base, such as in areas above the bone/tendon, oxygen delivery from the lateral edges of the scaffold is important. This study compared the oxygen permeability of skin scaffolds, currently commercially available in Turkey (Nevelia®, MatriDerm®, and Pelnac®), in the lateral plane. To measure oxygen permeability, an interconnected closed system was created. Oxygen permeability was evaluated based on the color change that occurred as a result of the reaction of iron with oxygen. After the dermal matrices placed in the closed system were exposed to oxygen, the color change on the surface of the dermal matrices was measured, and electron microscopic images were recorded to compare deformation before and after the procedure. Two scaffolds did not show deformation after the procedure while Pelnac® had minimal deformation. The oxygen rates on the nitrogen side of the test apparatus were found to be 29%, 34%, and 27% for Nevelia®, MatriDerm®, and Pelnac®, respectively; and the oxygen transmission lengths (length of color change) of these scaffolds in the lateral plane were 1, 2, and 0.5 cm, respectively. Although none of the scaffolds showed significant deformation, and all continued to exhibit their scaffold properties after the procedure, MatriDerm® was determined to be the most suitable scaffold for use in avascular areas, with a 2-cm oxygen transmission length in terms of lateral oxygenation. • A celluar dermis and artificial dermal matrices have developed and used for full-thickness skin loss. • Oxygen is required for cell migration in to the skin scaffold. • Oxygen transmission along the surfaces of skin scafolds should be focused. • MatriDerm was determined to be the most suitable scaffold for use in avascular areas. [ABSTRACT FROM AUTHOR]

This article discusses the clinical features of atopic dermatitis (AD) in pediatric patients with skin of color (SOC) and compares them to non-SOC patients. AD is a common inflammatory skin disease that affects both industrialized and low-income countries. The study found that AD in SOC patients often presents with intense xerosis, nummular eczema, prurigo nodularis-type lesions, and extensor site eczema. These features may be underestimated and should be adequately described and addressed in order to provide better care for SOC patients. The study highlights the need for a more complete understanding of AD in diverse populations. [Extracted from the article]

Atopic dermatitis (AD)/atopic eczema is a chronic relapsing inflammatory skin disease affecting nearly 14% of the adult population. An important pathogenetic pillar in AD is the disrupted skin barrier function (SBF). The atopic stratum corneum (SC) has been examined using several methods, including Raman microspectroscopy, yet so far, there is no depth-dependent analysis over the entire SC thickness. Therefore, we recruited 21 AD patients (9 female, 12 male) and compared the lesional (LAS) with non-lesional atopic skin (nLAS) in vivo with confocal Raman microspectroscopy. Our results demonstrated decreased total intercellular lipid and carotenoid concentrations, as well as a shift towards decreased orthorhombic lateral lipid organisation in LAS. Further, we observed a lower concentration of natural moisturising factor (NMF) and a trend towards increased strongly bound and decreased weakly bound water in LAS. Finally, LAS showed an altered secondary and tertiary keratin structure, demonstrating a more folded keratin state than nLAS. The obtained results are discussed in comparison with healthy skin and yield detailed insights into the atopic SC structure. LAS clearly shows molecular alterations at certain SC depths compared with nLAS which imply a reduced SBF. A thorough understanding of these alterations provides useful information on the aetiology of AD and for the development/control of targeted topical therapies. [ABSTRACT FROM AUTHOR]

New transdermal biosensors measure analytes that diffuse from the bloodstream through the skin, making it important to reduce the system response time and understand measurement output. While highly customized models have been created for specific sensors, a generalized model for transdermal sensor systems is lacking. Here, a simple one-dimensional diffusion model was used to characterize the measurement system and classify biosensors as either flux types or concentration types. Results showed that flux-type sensors have significantly faster response times than concentration sensors. Furthermore, flux sensors do not measure concentration, but rather have an output measurement that is proportional to skin permeability. These findings should lead to an improved understanding of transdermal measurements and their relation to blood analyte concentration. In the realm of alcohol research, where the majority of commercially available sensors are flux types, our work advocates toward moving away from transdermal alcohol concentration as a metric, and instead suggests embracing transdermal alcohol flux as a more suitable alternative. [ABSTRACT FROM AUTHOR]

Introduction: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. Methods: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. Results: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products. Conclusion: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions. [ABSTRACT FROM AUTHOR]

NRF2 is a master regulator of the cellular protection against oxidative damage in mammals and of multiple pathways relevant in the mammalian aging process. In the epidermis of the skin NRF2 contributes additionally to the formation of an antioxidant barrier to protect from environmental insults and is involved in the differentiation process of keratinocytes. In chronological aging of skin, the capacity for antioxidant responses and the ability to restore homeostasis after damage are impaired. Surprisingly, in absence of extrinsic stressors, NRF2 deficient mice do not show any obvious skin phenotype, not even at old age. We investigated the differences in chronological epidermal aging of wild type and NRF2‐deficient mice to identify the changes in aged epidermis that may compensate for absence of this important transcriptional regulator. While both genotypes showed elevated epidermal senescence markers (increased Lysophospholipids, decreased LaminB1 expression), the aged NRF2 deficient mice displayed disturbed epidermal differentiation manifested in irregular keratin 10 and loricrin expression. The tail skin displayed less age‐related epidermal thinning and a less pronounced decline in proliferating basal epidermal cells compared to the wildtype controls. The stratum corneum lipid composition also differed, as we observed elevated production of barrier protective linoleic acid (C18:2) and reduced abundance of longer chain saturated lignoceric acid (C24:0) among the stratum corneum fatty acids in the aged NRF2‐deficient mice. Thus, despite epidermal differentiation being disturbed in aged NRF2‐deficient animals in homeostasis, adaptations in keratinocyte proliferation and barrier lipid synthesis could explain the lack of a more severe phenotype. [ABSTRACT FROM AUTHOR]

Rose Bengal (RB) is a fluorescent dye with several potential biomedical applications, particularly in dermatology. Due to RB's poor physicochemical properties, several advanced delivery systems have been developed as a potential tool to promote its permeation across the skin. Nevertheless, no validated quantitative method to analyse RB within the skin is described in the literature. Considering RB exhibits a conjugated ring system, the current investigation proposes fluorescence-based techniques beneficial for qualitatively and quantitatively determining RB delivered to the skin. Notably, the development and validation of a fluorescence-coupled HPLC method to quantify RB within the skin matrix are herein described for the first time. The method was validated based on the ICH, FDA and EMA guidelines, and the validated parameters included specificity, linearity, LOD, LLOQ, accuracy and precision, and carry-over and dilution integrity. Finally, the method was applied to evaluate RB's ex vivo permeation and deposition profiles when loaded into dermatological formulations. Concerning qualitative determination, multiphoton microscopy was used to track the RB distribution within the skin strata, and fluorescence emission spectra were investigated to evaluate RB's behaviour when interacting with different environments. The analytical method proved specific, precise, accurate and sensitive to analyse RB in the skin. In addition, qualitative side-analytical techniques were revealed to play an essential role in evaluating the performance of RB's dermatological formulation. [ABSTRACT FROM AUTHOR]

Objectives: To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method. Methods: Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure. Results: Mechanical simulations resulted in skin stretching and thinning (20%–26% hair follicle diameter increase, and 21%–27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 μg ∙ cm−2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 μg ∙ cm−2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from ∼ 10 μm2 ∙ s−1 to between 200–500 μm2 ∙ s−1. Conclusions: Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation. [ABSTRACT FROM AUTHOR]

Various types of skin disorders across each age group and in each part of geographical world are very dreadful. Despite not being fatal each time they are always of social and mental concern for suffering individuals, causing complications in millions of patients every day and require comparatively longer duration of treatment. Off late, various topical/transdermal formulations have been widely explored for the treatment of various skin ailments. The efficiency of topical therapy depends on various physiochemical properties of drugs like particle size, particle size distribution, partition coefficient, viscosity of dosage form, skin permeability, skin condition and the site of application. Therefore, in plenty of examples, long-acting topical formulations have shown to be markedly excellent in comparison to conventional dosage forms. The major advantages of topical formulations accrue from their demonstrated ability: (i) Reduced serious side effects that may occur due to undesirably higher systemic absorption of drug. (ii) Enhancement of drug accumulation at the desired site. (iii) Easy incorporation of enormous range of hydrophilic and hydrophobic drugs and (iv) Reduced risk of dose dumping and comparatively easy termination of drug release. The prospective applications of topically applied formulations and the deposition of pharmaceuticals into the skin are examined. [ABSTRACT FROM AUTHOR]