SKIN PHARMACOLOGY AND PHYSIOLOGY

Bioavailability of Hydroquinone from Topical Formulations: A Product Comparison Study using the In Vitro Permeation Test (IVPT)
Lehman PA and Franz TJ
Introduction The In Vitro Permeation Test (IVPT) is considered to be an important tool for assessing the topical pharmacokinetics of dermatologic formulations. An IVPT study evaluating products that contain the skin bleaching agent, hydroquinone (HQ), as the active ingredient, is presented in support of the value of IVPT in comparing the relative bioavailability of HQ products from different commercial products. Methods Ten former OTC and Rx products were evaluated for in vitro bioavailability using human ex vivo skin in Franz diffusion cells. In addition, to assess the correlation between in vitro and in vivo absorption, the suction blister technique was used to determine HQ concentration in interstitial fluid from two products differing in HQ bioavailability. Results Significant differences in HQ absorption between products were found. Total absorption varied from 27 to 279 g/cm2/48 hrs, and neither total absorption nor the rates of absorption were found to correlate with labeled drug concentration. In vivo suction blister data on two products were in accordance to the IVPT results. Discussion Overall, this study demonstrates the sensitivity and value of the IVPT method for detecting differences in the pharmacokinetics of topical formulations containing a single therapeutic agent but which differ in formulation design.
Intake of soymilk-okara powder for 8 weeks induced the improvement of skin elasticity in Japanese women
Maeta A, Katsukawa M, Hayase Y and Takahashi K
Soymilk-okara, a rich source of protein and dietary fiber, is a byproduct of soymilk manufacturing. We investigated whether soymilk okara intake improved skin conditions in Japanese women with self-reported constipation.
Effects of two different basic skin care regimens on children and adult skin microbiota: an exploratory randomized controlled crossover trial
Hillmann K, Tomova-Simitchieva T, Pinta PS, Xiong Z, Moter A, Kanti-Schmidt V, Kottner J and Blume-Peytavi U
Regular use of leave-on skin care products has positive effects on the skin barrier and appears to influence the skin microbiome in atopic dermatitis (AD). However, product-related effects on the skin microbiome are unclear. The aim of this study was to investigate to which extent the application of an emollient plus product differs from a petrolatum-based basic skin care product in terms of skin physiology, skin barrier and skin microbiome. In an exploratory study regime fifty subjects (children and adults) with mild AD were randomized to receive Bepanthen SensiDaily® (BSD) and Basiscreme DAC (DAC) for three months in a cross-over design. Skin physiological measurements and skin microbiome swabs were taken on the forearm and lower leg before and after each 3-month application period of the respective product. Improvement of skin physiological parameters after 3 months was observed in both topical leave on product groups. Statistically significant differences were observed in baseline microbiomes between children and adults (p<0.001) but not between the product groups. Regular application of leave-on products leads to better stratum corneum hydration after 3 months with better effects of BSD on the forearms of children and the lower legs of adults compared to DAC. The application of BSD and DAC did not lead to significant alterations in the overall composition of the skin microbiome. Although there were shifts in the frequency of certain microbial genera, these changes were not consistent between age groups and treatments.
Emulsifier-induced changes to the human skin barrier - Connection to ceramide profiles and assessment as a skin lesion model
Reuter M, Schoenfelder H, Gaiser A, Volc S and Lunter D
Emulsifiers are common excipients in dermal products stabilizing formulations such as creams and emulsions. But due to their potential for skin irritation, emulsifiers for pharmaceutical use should be tested regarding their tolerability before introducing them to the skin of patients. In this study, a systematic investigation with six oil in water (o/w)-emulsifiers was performed on the forearms of 12 healthy human volunteers, six female and six male. We analyzed the effects of pharmaceutical emulsifiers on the macroscopic skin health parameters measured as trans-epidermal water loss (TEWL) and skin hydration and measured the ceramide profile of the treated skin sites using liquid chromatography coupled to mass spectrometry (LC-MS) in order to assess the skin tolerability of the investigated emulsifiers. In a second step, a Partial Least Squares Regression was employed to investigate relationships between changes in the ceramide profile to changes in the TEWL of skin treated with a non-ionic as well as an anionic emulsifier. Skin health measurements showed that the applied emulsifiers inflicted no significant changes compared to the water-treated sample, demonstrating a remarkable skin tolerability. The employed regression model showed a good fit as well as adequate prediction and identified ceramide species associated with impaired skin barrier function. Furthermore, it was found that the relationship between the ceramide profile and the skin barrier function in emulsifier-induced skin damage shows distinct similarities to the interplay of ceramides and skin barrier function in lesional skin linked to Atopic Dermatitis (AD), hinting towards a common underlying mechanism and opening up possibilities to simulate disease-related changes to the skin for the development of skin damage models. In conclusion, these detailed investigations yield insight into possible mechanisms of emulsifier induced skin damage and show its versatility in the investigation of pharmaceutical emulsifiers for formulation development as well as basic research.
Healing Diabetic Foot Ulcers with Topical Timolol Improves Healed Epithelial Integrity
Lyle RE, Dafinone ME, Lim P, Budhiraja A, Mehta A, Dahle SE and Isseroff RR
Diabetic foot ulcers are a common complication in diabetes, leading to high amputation risk and significant healthcare costs. Given topical timolol's emergence as a potential wound-healing agent, our study explored its impact on epidermal integrity.
Skin Transcriptomic Analysis Reveals Altered Fatty Acid Metabolism Pathways in Mice Subjected to Sleep Fragmentation
Lee DB, Yoo SL, Heo JS, Lim JY, Pyo SS, Moon JS, Lee MR, Kim J, Kim SW and Yoon DW
Sleep fragmentation (SF) is a hallmark of sleep disorders and has been associated with systemic health issues, but its specific impact on skin health remains unclear. This study aimed to investigate whether SF impairs skin barrier function and identify the biological pathways involved in SF-induced skin damage.
In vitro Antibacterial and Antifungal Activity of a Skin Ointment and Its Active Pharmaceutical Ingredients Larch Turpentine, Turpentine Oil, and Eucalyptus Oil
Pianta E, Günnewich N, Zimmermann C, Petrini O, Diaz-Miyar J and Fragoso-Corti C
Turpentine derivatives and eucalyptus oil are herbal substances traditionally used to treat various skin infections. Limited non-clinical data suggest they exert an immunological activity, but only scant information exists on their antibiotic effects. This in vitro study has been carried out to investigate the antibacterial and antifungal activity of a marketed skin ointment; its active pharmaceutical ingredients larch turpentine, eucalyptus oil, and turpentine oil; and their mixture, against bacteria and yeasts commonly present on the skin and causing skin infections.
Reflectance Confocal Microscopy of Dermal Papillae in Healthy Skin: A Histopathology Controlled Study
Lacarrubba F, Verzì AE, Misciali C, Domenicali D and Micali G
Previous studies have investigated the density of dermal papillae (DP) in normal skin using reflectance confocal microscopy (RCM), a noninvasive imaging technique that allows a real-time, high-resolution imaging of the skin, although no histological confirmation was provided. The aim of the present study was to compare the RCM evaluation of DP density in healthy skin with horizontal histopathological sections (HHS), a technique that provides a horizontal view of the skin.
How to Choose an Emollient? Pharmaceutical and Sensory Attributes for Product Selection
Huber P, Reinau D, Brodard Z, Meier CR and Surber C
Emollients are part of daily body care and have become indispensable therapeutic adjuvants for the treatment of dry skin conditions. Adherence to topical treatments, notably for dry skin conditions, has been reported to be low. The underlying reasons may include insufficient medical and nursing support for product selection, specific product attributes, aspects of product application, and product feel on the skin. Attempts have also been made to portray lipid content, galenic product format, or rheological attributes (pharmaceutical attributes) as adherence-promoting or adherence-preventing properties. In the treatment of dry dermatoses with emollients, there is little information describing and relating to these various features. We explored whether the sensory attributes of selected emollients were associated with common product attributes such as lipid content, viscosity, or galenic product format and discuss the extent to which this information is useful for product selection.
miR-211 Regulates Cutaneous Wound Healing through Inhibiting Inflammatory Reactions and Oxidative Stress by Binding SOX11
Chen Y, Zhang X, Wu F, Wang L, Zuo H, Tian H and Chen H
Loss of skin integrity due to a wound or disease can lead to severe disability or even life threat. The highly expressed microRNAs in the skin are of great significance for skin development. The purpose of the investigation was to explore the effect and mechanism of miR-211 on inflammation, oxidative stress, and migration in keratinocytes.
The Role of Reactive Oxygen Species in the Pathogenesis of Alopecia Areata: A Systematic Review and Meta-Analysis
Perlmutter J, Akouris PP, Fremont S, Yang B, Toth E, Eze M and Wiseman M
Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear. This study investigates the potential role of reactive oxygen species in AA pathogenesis.
A Rigorously Simple Quantitative Model for Free Radical Behavior in Aerobic Biological Systems
Zastrow L, Lademann J, Meinke MC and Lohan SB
Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of reactive oxygen species (ROS) for °OH to over 10 s for lipid oxygen species (LOS), indicating that mixtures of free radicals form the basic components for these processes.
Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation
Shin KO, Ishida K, Mihara H, Choi Y, Park JH, Park SH, Hwang JT, Wakefield JS, Obata Y, Uchida Y and Park K
Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated.
Evaluation of Bioequivalence and Pharmacokinetic Profiles for Topical Desonide Cream Using Chinese Skins
Sun Y, Yang N, Huang J, Yao A, Ye L, Yang S, Xiao M, Zhang X, Ding J, Kuang Y, Zhou Y and Yang G
Skin-blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin-blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed.
Cluster Analysis Identifies Clinical Phenotypes of Primary Hyperhidrosis
Henning MAS, Jemec GBE, Pedersen OB and Taudorf EH
Identifying subgroups of patients with primary hyperhidrosis (PHH) can improve the understanding of the disease pathophysiology. The study objective was to determine the naturally occurring subgroups of patients with PHH based on clinical characteristics.
Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions
Ng SP, Bielfeldt S, Laing S, Danby S and Cork MJJ
Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin.
A Brief Review of Vehicles for Topical Therapies
Ahuja K, An M and Lio P
Topical therapy has been a fundamental part of dermatology, evolving from early ointments to advanced transdermal treatments. These formulations allow for effective management of skin conditions by maximizing local drug delivery and minimizing systemic effects. Modern topical therapies continue to benefit from innovations that improve both efficacy and patient outcomes.
Intraday Variations in Skin Water Parameters
Mayrovitz HN
Three interrelated skin water assessments include stratum corneum hydration (SCH) via electrical measurements, skin water using tissue dielectric constant (TDC) measurements, and transepidermal water loss (TEWL). These are differentially used for skin physiology research, clinical assessments of dermatological conditions and to assess skin water in diabetes and lymphedema. Often volar forearm skin is used for assessments done at various times of day (TOD). The present goal was to assess the extent of intraday variability in SCH, TDC, and TEWL.
A Consideration on Infinite and Finite Dosing in Skin Permeation Using Reconstructed Models
Saeki Y, Kato E and Tokudome Y
When vitamin derivatives penetrate the epidermis, they release active compound such as ascorbic acids (AsA) and tocopherols via enzymatic digestion of chemical modifiers. To determine the transdermal penetration of the derivatives, the total permeation of both the derivatives and their active compounds that released from the derivatives should be considered. In this study, we established a skin penetration test method using a cultured, reconstructed skin model with active epidermal enzymes. And we analyzed two vitamin derivatives with different chemical properties: magnesium ascorbyl phosphate (APM) and sodium tocopheryl phosphate (TPNa), both of which has been confirmed their skin permeation in the reconstructed models and the digestion to AsA and α-tocopherol by the epidermal enzymes, respectively.
How Individuals Apply and Perceive Sunscreen: Empirical Evidence from Germany
Keck C and Leyer M
This study explores how individuals in Germany use and perceive sunscreen, aiming to identify the factors that influence their sunscreen choices. The research focuses on key elements such as convenience, environmental awareness, openness to new technologies, and preferences for different sunscreen products.
In vivo Study to Evaluate an Intelligent Algorithm for Time Efficient Detection of Malignant Melanoma Using Dermatofluoroscopy
Weihmann K, Schleusener J, Eigentler TK, Ghoreschi FC, Moritz RKC, Szyc L, Dronnik E and Meinke MC
Dermatofluoroscopy is an optical noninvasive method of melanoma/nevus differentiation that has shown 89% sensitivity and 45% specificity in clinical trials, but long measurement duration hinders clinical use. An intelligent algorithm was developed to shorten the measurement time without compromising its diagnostic accuracy. It uses dermoscopic images of the skin lesions to be measured to select measurement points based on the assessment of color values.