Skin Pharmacology and Physiology最新文献

Introduction: Percutaneous drug delivery systems are attractive not only as a therapeutic strategy but also for cosmetic treatment. Iontophoresis is a well-recognized method for promoting transdermal absorption of ionized compounds. Franz cells are generally used to estimate drug permeation of skin by iontophoresis. However, methods using Franz cells are less versatile; for instance, the method is unsuited for use with a portable electric facial care device having a working probe of a certain size and weight. In this study, we constructed a semi-dry apparatus for use with an electric facial care device.

Methods: The apparatus has a multilayer structure consisting of mouse skin and 3 filter papers, modeled after the Franz cell. The skin permeation of the drug edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) was then measured using this apparatus.

Results: Edaravone permeation depended on working time, drug concentration, and ionization ratio of edaravone when iontophoresis was carried out with an electric facial care device. Furthermore, glycyrrhizic acid, α-tocopheryl phosphate, retinoic acid, and ascorbyl palmitate, which are recognized as functional cosmetic materials, also permeated the skin by applying iontophoresis with the device.

Conclusion: These results suggest that the developed measuring apparatus is applicable for use with a portable electric facial care device and that iontophoresis using a portable electric facial care device is potentially useful in the cosmetic field.

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.

Introduction: Several olfactory receptors (ORs) are expressed in human skin, where they regulate skin pigmentation, barrier function, wound healing, and hair growth. Previously, we found that the selective activation of OR family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® differentially stimulates the expression of antimicrobial peptides (AMPs) in human scalp hair follicle epithelium ex vivo. As OR2AT4 is also expressed by epidermal keratinocytes, we hypothesized that it may modulate intraepidermal AMP synthesis, thereby contributing to skin microbiome management.

Methods: We investigated this hypothesis in organ-cultured human skin in the presence of Sandalore® and antibiotics and evaluated epidermal production of two AMPs, LL37 (cathelicidin) and dermcidin (DCD), as well as OR2AT4, by quantitative immunohistomorphometry. Moreover, we quantified DCD secretion into the culture medium by ELISA and studied the effect of culture medium on selected bacterial and fungal strains.

Results: Topical application of Sandalore®to organ-cultured human skin increased OR2AT4 protein expression, the number of DCD-positive intraepidermal cells, and DCD secretion into culture media, without significantly affecting epidermal LL37 expression. In line with the significantly increased secretion of DCD into the culture medium, we demonstrated, in a spectrophotometric assay, that application of conditioned media from Sandalore®-treated skin promotes Staphylococcus epidermidis, Malassezia restricta, and, minimally, Cutibacterium acnes and inhibits Staphylococcus aureus growth.

Conclusion: In addition to demonstrating for the first time that DCD can be expressed by epidermal keratinocytes, our pilot study suggests that topical treatment of human skin with a cosmetic odorant (Sandalore®) has the potential to alter the composition of the human skin microbiome through the selective upregulation of DCD. If confirmed, Sandalore® could become an attractive adjuvant, nondrug treatment for dermatoses characterized by dysbiosis due to overgrowth of S. aureus and Malassezia, such as atopic dermatitis and seborrheic dermatitis.

Introduction: Heparin is a commonly used anti-coagulant administered either by intravenous or subcutaneous injection for a systemic effect or topically for the treatment of peripheral vascular disorders.

Objective: This study aimed to formulate heparin in non-ionic colloidal carrier systems (CCSs) having enhanced percutaneous absorption for systemic and topical administration.

Methods: Five CCSs were developed and characterized for their rheological properties, droplet size, and drug loading. The percutaneous absorption of heparin was evaluated in vitro using Franz diffusion cells with rats' skin and with the aid of a developed high-pressure chromatography method. Furthermore, the efficacy of two developed heparin CCSs was tested percutaneously in rats by measuring the response against the time in comparison to subcutaneous administration.

Results: The rheograms and droplet size measurements showed that the developed drug delivery systems have Newtonian properties with a droplet size between 109 and 460 nm. As much as 500 mg of heparin could be loaded in around 5 mL of CCS. Furthermore, using Franz diffusion cells, a diffusion rate of 19.216 ± 2.01 USP U/cm2.h could be achieved for heparin-loaded CCSs. Moreover, the estimated percutaneous in vivo relative bioavailability in comparison to subcutaneous administration could reflect that at least more than 50% of the drug passed through the skin.

Conclusion: The developed novel non-toxic CCSs containing heparin can be good candidates for percutaneous administration as alternative delivery systems for subcutaneous and intravenous invasive administration.

Introduction: Tumor necrosis factor (TNF)-α released after follicular injury such as that caused by plucking plays a role in the activation of hair regeneration. Microneedle (MN) treatment is applied to the scalp to increase permeability and facilitate the delivery of any number of compounds. Because the MN treatment causes injury to the epidermis, albeit minor, we reasoned that this treatment would lead to a temporary TNF-α surge and thereby promote hair regeneration.

Methods: To investigate the effects of MN-treatment-induced microinjury and TNF-α on hair growth, we used C57BL/6N mice which were divided into six experimental groups: three groups of 1) negative control (NC), 2) plucking positive control (PK), and 3) MN therapy system (MTS) mice; and three groups identical to above were treated with a TNF-α blocker for 3 weeks: 4) NCB, 5) PKB, and 6) MTSB group.

Results: After injury, TNF-α surge occurred on day 3 in the PK group and on day 6 in the MTS group. Wnt proteins and VEGF expression were markedly increased in the PK group on day 3 and on day 6 in the MTS group compared to the NC group. Following wound healing, only MTS and PK groups displayed thickened epidermis and longer HF length. Within the 2 weeks following treatment, the rate of hair growth was much slower in the injured mice treated with the TNF-α blocker.

Conclusion: Our findings indicate that microinjury stimulates the wound-healing mechanism via TNF-α/Wnt/VEGF surge to induce hair growth, and that blocking TNF-α inhibits this growth process.

Background: Skin care is a basic, daily activity performed by formal and informal caregivers from birth until end of life. Skin care activities are influenced by different factors, e.g., culture, knowledge, industrial developments and marketing activities. Therefore, various preferences, traditions, and behaviors exist worldwide including skin care of neonates and infants. The objective of this scoping review was to obtain an overview about the evidence of skin care activities in neonates and infants. Studies from 2010 were eligible if the population was (skin) healthy neonates and infants; if the concept was skin care interventions; and if the context was at home, in a community setting, in a pediatric outpatient service, or in a hospital. We searched for the literature via OVID in MEDLINE and Embase, in the Cochrane Library, in trial registries and for gray literature.

Summary: We identified 42 studies since 2010, which examined four main skin care interventions: bathing, wiping, washing, and topical application of leave-on products. Details of interventions were often not reported, and if they were, they were not comparable. The four skin care interventions focused on 13 different care goals, mainly prevention of skin diseases, maintaining skin barrier function, and improving (skin) health. We evaluated effects of skin care interventions using 57 different outcome domains; 39 of 57 were skin-related and 18 were not. Mostly, laboratory or instrumental measurements were used.

Key messages: Our scoping review identified four skin care interventions with a broad heterogeneity of product categories and application details. Studies in skin care interventions should include all relevant information about product category and application details to ensure comparability of study results. This would be helpful in developing recommendations for formal and informal caregivers. We identified 13 skin care goals. "Maintaining healthy skin/skin barrier function/skin barrier integrity," "prevention of atopic dermatitis," "cleansing," and "improving skin barrier function" were most often allocated to skin care interventions. There is substantial variability regarding outcome domains in skin care research. Our results support the need of developing core outcome sets in the field of skin care in healthy skin, especially in this age-group of neonates and infants.

Introduction: The use of epicutaneously applied permethrin in the treatment of common scabies is considered to be the first-line therapy. Due to increasing clinical treatment failure, the development of genetic resistance to permethrin in Sarcoptes scabiei var. hominis has been postulated. In addition, metabolic resistance and pharmacokinetic limitations by parasitic digestion and reactive thickening of stratum corneum are suspected to cause a reduction in cutaneous bioavailability.

Methods: Since lipophilic permethrin is known to form hydrophobic interactions with proteins via van der Waals interactions, a similar interaction was assumed and investigated for permethrin and the protein keratin. Using keratin particles extracted from animal material, a model for hyperkeratotic and parasitic digested scabies skin was developed. Using fluorescence-labeled keratin and ³H-permethrin, their interaction potential was validated by loading and unloading experiments. Additionally, the impact of keratin to permethrin penetration was investigated based on an in vitro model using Franz diffusion cells.

Results: For the first time, keratin particles were introduced as a model for dyskeratotic skin, as we were able to show, the keratin particles' interaction potential with permethrin but no penetration behavior into the stratum corneum. Moreover, comparative penetration experiments of a reference formulation with and without added keratin or keratin-adherent permethrin showed that keratin causes a steal effect for permethrin, leading to a relevant reduction in cutaneous bioavailability in the target compartment.

Conclusion: The results provide further evidence for a relevant pharmacokinetic influencing factor in the epicutaneous application of permethrin and a rationale for the necessity of keratolytic pretreatment in hyperkeratotic skin for the effective use of topical permethrin application in scabies.

Introduction: Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis.

Methods: Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient's global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording.

Results: A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events.

Conclusion: The turpentine ointment is an effective and safe option for the treatment of folliculitis.

Background: A disruption of sebocyte differentiation and lipogenesis has fatal consequences and can cause a wide spectrum of skin diseases, from acne vulgaris to sebaceous carcinoma, however, the relevant molecular mechanisms have not been fully clarified.

Objectives: The induction of autophagy and apoptosis in human sebocytes in response to biologically relevant fatty acids was investigated.

Methods: Free fatty acids (arachidonic acid, linoleic acid, palmitic acid, and palmitoleic acid) and the pan-caspase inhibitor QVD-Oph were added to the supernatant of cultured human SZ95 sebocytes. Individual relevant proteins were analyzed by Western blotting. Apoptosis and cell viability were determined, and typical autophagy structures were detected through electron microscopy. To obtain cell growth curves, cell confluence was continuously monitored by real-time cell analysis.

Results: Fatty acids induced the development of intracellular lipid droplets with subsequent apoptosis, whereas arachidonic acid caused the most rapid effect. Cleavage products of caspase-3 were only detected in arachidonic acid-induced apoptosis. The high basal apoptotic rate of cultured SZ95 sebocytes was strongly suppressed by QVD-Oph. Fatty acid-induced apoptosis was also markedly inhibited by QVD-Oph, whereas intracellular lipid droplets further accumulated. While cell viability after incubation with linoleic acid, palmitic acid, or palmitoleic acid and QVD-Oph was comparable with that of non-treated controls, arachidonic acid significantly reduced cell viability and cell density despite the concomitant pan-caspase inhibitor treatment. Using electron microscopy, typical autophagy structures were detected, such as autophagosomes and autolysosomes, at the basal level, which became more pronounced after treatment with fatty acids.

Conclusions: Our findings contribute to a better understanding of the inflammation-associated mechanisms of lipogenesis and cell death induction in human sebocytes and may help to unveil the effects of fatty acid-rich human nutrition.

Introduction: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases.

Methods: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test.

Results: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated.

Conclusion: CAP is a promising new treatment of rosacea, especially for PPR.