Frequent oil baths and skin barrier during infancy in the PreventADALL study.

BACKGROUND: In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established. OBJECTIVES: The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect. METHODS: Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8 months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12 months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries. RESULTS: The TEWL (95% confidence interval) was on average 0.42 g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3 months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12 months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3 months (59% vs. 51%) and at 6 months of age (63% vs. 53%), while at 12 months of age, the difference was no longer significant. At 3 months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life. CONCLUSIONS: Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age, while the skin at 3 and 6 months appeared less dry in infants subjected to the skin intervention.

Atopic dermatitis (AD) affects approximately 20% of children in industrialized countries. AD causes dry, itchy skin and can increase the chance of infections. This study was a substudy of the large Scandinavian PreventADALL trial, including 2394 infants, recruited from the general population between 2014 and 2016. Children in this trial were allocated randomly to receive either a skin intervention, food intervention, combined intervention, or no intervention. Children were examined at 3, 6 and 12 months of age. The examinations involved an investigation of the skin, to evaluate dry skin and skin barrier function by transepidermal water loss (TEWL) in the outer layers of the skin (higher TEWL suggests decreased skin barrier function). The skin intervention consisted of oil baths at least 4 times per week from 2 weeks of age through 8 months of age, and have previously not been shown to prevent AD by 1 and 3 years of age. We aimed to investigate whether frequent oil baths had any effect on TEWL and dry skin. We found that the skin intervention increased TEWL in the first year of life, especially at 3 months of age. Dry skin was less common in the skin intervention groups compared with the groups with no skin intervention. Infants with mutations in the gene coding for a skin barrier protein, called filaggrin, were associated with increased TEWL; however, in the skin intervention group, TEWL was similar among the infants with or without filaggrin mutations. Our findings suggest that oil baths several times per week from early infancy transiently decreases skin barrier function.

Double-blind, vehicle-controlled clinical investigation of peptide OS-01 for skin rejuvenation.

INTRODUCTION: Senescent cells contribute to age-related tissue deterioration, including the skin, which plays important roles in overall health and social interactions. This study aimed to assess the effects of the senotherapeutic peptide, OS-01 (a.k.a. Pep 14), on skin. METHODS: A 12-week split-face, double-blinded, vehicle-controlled study involving 22 participants was conducted. The OS-01-containing formulation was applied to one side of the face, while the other side received an identical control formulation lacking the peptide. Skin characteristics were assessed using instrumental measurements, expert clinical grading, and subjective questionnaires. RESULTS: Results showed that the OS-01 formulation significantly improved one aspect of skin barrier function, as evidenced by reduced trans-epidermal water loss compared to both baseline and vehicle control. Expert grading and Antera 3D image analysis revealed a reduction in wrinkle appearance and indentation in the periorbital area, and improved skin texture and radiance on both sides of the face, with the OS-01-containing formulation demonstrating superior results. Participants also perceived improvements in skin hydration, smoothness, radiance, and overall appearance. CONCLUSION: The findings suggest that the OS-01 formulation promotes skin health by strengthening the skin barrier, protecting against dehydration, reducing the appearance of wrinkles, and improving skin texture and radiance. These effects are likely attributed to the senotherapeutic properties of OS-01 in reducing cellular senescence and its associated detrimental effects.

Silicone based water-in-oil emulsion fortified with anthocyanin: In-vitro, in-vivo study.

Skin care formulations with antioxidants are being widely explored for their benefits to human skin. The purpose of this study was to formulate a stable w/o emulsion containing anthocyanin derived from Malus dosmestica fruit extract and to further explore its beneficial effects on normal human skin. Anthocyanin was extracted using various solvents from the peel of Malus dosmestica fruit. w/o creams containing anthocyanin has been prepared and systematically characterized for various physiochemical properties in terms of stability at varying conditions of storage. An efficacy study has been carried out on 12 male healthy Asian subjects to determine effects of anthocyanin on skin melanin, erythema, skin moisture, trans-epidermal water loss (TEWL) and on skin sebum. Solvent system containing methanol/acetone/water (3.5: 3.5: 3 v/v/v) including 1% formic acid established a best recovery of anthocyanin from fruit peel. W/O emulsions presented promising stability profile when kept at different storage conditions over 90 days period. All skin parameters studied, anthocyanin has been found more efficacious (p<0.05) for its effects on skin melanin and erythema content of skin. It has been shown that a topical application of anthocyanin derived from Malus domestica has substantial potential for human skin system and needs some patient oriented studies could warrant its potential for damaged skin.

Antioxidant and Cytoprotective Properties of Plant Extract from Dry Flowers as Functional Dyes for Cosmetic Products.

Nowadays, natural dyes are expected by the cosmetic and food industries. In contrast to synthetic dyes, colorants derived from natural sources are more environmentally friendly and safer for human health. In this work, plant extracts from Gomphrena globasa L., Clitoria ternatea L., Carthamus tinctorius L., Punica granatum L. and Papaver rhoeas L. as the natural and functional dyes for the cosmetics industry were assessed. Cytotoxicity on keratinocyte and fibroblast cell lines was determined as well as antioxidant and anti-aging properties by determining their ability to inhibit the activity of collagenase and elastase enzymes. In addition, the composition of the extracts was determined. The obtained extracts were also applied in face cream formulation and color analyses were performed. It has been shown that the obtained extracts were characterized by no cytotoxicity and a high antioxidant potential. The extracts also show strong ability to inhibit the activity of collagenase and moderate ability to inhibit elastase and provide effective and long-lasting hydration after their application on the skin. Application analyses showed that the extracts of P. rhoeas L., C. ternatea L. and C. tinctorius L. can be used as effective cosmetic dyes that allow for attainment of an intense and stable color during the storage of the product. The extracts of P. granatum L. and G. globasa L., despite their beneficial effects as active ingredients, did not work effectively as cosmetic dyes, because cosmetic emulsions with these extracts did not differ significantly in color from emulsions without the extract.

Vehicle Effects on the Rosacea Skin Barrier.

BACKGROUND: Inflammatory papulopustular rosacea produces sensitive facial skin. Thus, medications designed for rosacea require careful vehicle development to insure optimal drug delivery in an environment suitable for barrier repair. OBJECTIVE: The objective of this phase 1 study was to elucidate the barrier effects of an investigational topical minocycline anhydrous gel 3% in subjects with inflammatory rosacea. METHODS: 31 male or female subjects with all complexion types and moderate facial rosacea, defined as 15+ inflammatory facial lesions, were enrolled in this single-site study to evaluate the effects of an investigational topical 3% minocycline anhydrous gel vehicle on skin barrier function; the new topical minocycline gel is an investigational product under development and has completed a phase 2b study in rosacea patients. Following a 30-minute acclimation period, subjects underwent a one-minute transepidermal water loss (TEWL) measurement on the left cheek and triplicate pin probe corneometry measurements from the right cheek. Subjects used the investigational topical 3% minocycline anhydrous gel every evening and returned to the research center at day 1, week 2, and week 4. RESULTS: 30/31 subjects completed the research study. The study medication produced a 23% (P=0.003) increase in skin hydration at day 1 and maintained the hydration increase with a 22% (P=0.003) increase at week 2 and a 20% increase (P=0.001) at week 4. Simultaneously, skin barrier function also improved with an 11% reduction in TEWL at day 1 followed by an 18% reduction in TEWL at week 2 (P=0.001) and a 28% decrease in TEWL at week 4 (P<0.001). This improvement in skin barrier was due to a combination of skin healing and the moisturizing properties of the investigational topical 3% minocycline anhydrous gel medication evaluated in this study. CONCLUSION: The investigational topical 3% minocycline anhydrous gel decreases TEWL, indicating barrier repair, while increasing corneometry measurements, indicating improved skin hydration. J Drugs Dermatol. 2021;20(6):630-632. doi:10.36849/JDD.6105Visit the rosacea resource center.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products. METHODS: Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review. RESULTS: Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances. CONCLUSIONS: The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

ARTICLE: Efficacy of Ceramide-Containing Formulations on UV-Induced Skin Surface Barrier Alterations.

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E.

Eczematous Drug Eruptions.

Eczematous drug eruptions are a heterogenous group of skin reactions that resemble eczema both clinically and histologically. We reviewed the literature and cataloged the systemically administered medications that cause these eruptions, along with their characteristic clinical presentations. We identified three primary pathophysiologic etiologies: (1) cutaneous immunomodulation, (2) skin dehydration, and (3) delayed hypersensitivity. Notably, eczematous eruptions caused by altered immunity in the skin may be increasing in incidence as some responsible drugs, in particular biologic therapies (such as tumor necrosis factor-α and interleukin-17 inhibitors) and targeted cancer treatments (including immune checkpoint inhibitors and epidermal growth factor receptor inhibitors), become more commonly employed in clinical practice. Other notable causes of eczematous eruptions include antiviral agents for hepatitis C virus and cardiovascular medications in elderly individuals, and notable subtypes of eczematous reactions include systemic contact dermatitis and photoallergic reactions, which are also discussed. The diagnostic gold standard is drug rechallenge and most reactions may be treated effectively with emollients, topical corticosteroids, and oral antihistamines.

Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution.

Chlorhexidine digluconate (CHG) is a cationic bisbiguanide used in the UK as the first-line skin antiseptic prior to surgery in the UK due to its favourable efficacy and safety profile, high affinity for skin binding and minimal reports of resistance. Despite this, bacteria remain within deeper skin layers, furrows and appendages that are considered inaccessible to CHG, due to its poor dermal penetration. In this study a third generation, polyamidoamine dendrimer (G3 PAMAM-NH2) was utilised to improve dermal penetration of CHG. A topical gel formulation was optimised to maximise CHG delivery (containing 0.5% gelling agent and 4% drug), followed by drug and dendrimer co-formulation into a commercially viable gel. The gel containing 4% CHG and 1 mM PAMAM dendrimer significantly increased the depth permeation of CHG compared to the commercial benchmark (Hibiscrub®, containing 4% w/v CHG) (p < 0.05). The optimised formulation was further characterised using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), which indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by commercial CHG formulations. This study therefore indicates that a G3 PAMAM-NH2 dendrimer gel may be viable as a permeation enhancer of CHG, for improved skin antisepsis in those at risk of a skin or soft tissue infection as a result of surgical intervention.

Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin.

BACKGROUND: Patients with sensitive skin find topical retinoid use for anti-aging purposes challenging due to irritation. Bakuchiol, a meroterpene from the Psoralea corylifolia seed, has retinol functionality through retinol-like regulation of gene expression. OBJECTIVE: This research examined the tolerability, efficacy, and barrier effects of a nature-based bakuchiol-containing cleanser and moisturizer in subjects with sensitive skin. METHODS: 60 female subjects Fitzpatrick skin types I–V age 40–65 years with sensitive mild to moderate photodamaged skin were enrolled in this 4 week study. A sensitive skin panel was constructed: 1/3 eczema/atopic dermatitis, 1/3 rosacea, 1/3 cosmetic intolerance syndrome. Subjects used a nature-based cleanser and moisturizer twice daily and underwent transepidermal water loss (TEWL), corneometry, tolerability assessments, and efficacy assessments at baseline, 5–10 minutes post-application, and week 4. RESULTS: The skin care products were well tolerated and efficacious (P<0.001) in terms of investigator assessed improvement in visual smoothness, tactile smoothness, clarity, radiance, overall appearance, and global anti-aging. Cheek corneometry measurements demonstrated a statistically significant 16% increase in skin moisture content (P<0.001). CONCLUSION: A bakuchiol nature-based anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin.J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5522.

Self-selected fluid volume and flavor strength does not alter fluid intake, body mass loss, or physiological strain during moderate-intensity exercise in the heat.

INTRODUCTION: The purpose of this study was to determine the effects of ad libitum flavor and fluid intake on changes in body mass (BM) and physiological strain during moderate intensity exercise in the heat. METHODS: Ten subjects (24±3yrs, 7M/3F) performed 60 min of treadmill walking at 1.3 m/s and 7% grade in an environmental chamber set to 33 °C and 10% relative humidity while carrying a 22.7 kg pack on two different occasions. Subjects consumed either plain water or water plus flavor (Infuze), ad libitum, at each visit. Pre and post exercise, fluid consumption (change in fluid reservoir weight) and BM (nude) were measured. During exercise, heart rate (HR), systolic blood pressure (SBP), rate of perceived exertion (RPE), oxygen consumption (VO2), respiratory exchange ratio (RER), core temperature (TC), and physiological strain index (PSI) were recorded every 15 min during exercise. RESULTS: No significant differences were observed for fluid consumption between fluid conditions (512 ± 97.2 mL water vs. 414.3 ± 62.5 mL Infuze). Despite a significant decrease from baseline, there were no significant differences in overall change of BM (Δ -1.18 vs. -0.64 Kg) or percent body weight loss for water and Infuze conditions, respectively (1.58 ± 0.6 and 0.79 ± 0.2%). Furthermore, there were no significant differences in HR (144 ± 6 vs. 143 ± 8 bpm), SBP (157 ± 5 vs. 155 ± 5 mmHg), RPE, VO2 (27.4 ± 0.9 vs. 28.1 ± 1.2 ml/Kg/min), RER, TC (38.1 ± 0.1 vs. 37.0 ± 0.1 °C), and peak PSI (5.4 ± 0.4 vs. 5.7 ± 0.8) between conditions. CONCLUSIONS: Offering individuals the choice to actively manipulate flavor strength did not significantly influence ad libitum fluid consumption, fluid loss, or physiological strain during 60 min of moderate intensity exercise in the heat.

Administration of Apple Polyphenol Supplements for Skin Conditions in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20-39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women.

Air Particulate Matter Induces Skin Barrier Dysfunction and Water Transport Alteration on a Reconstructed Human Epidermis Model.

Knowing the damage that particulate matter (PM) can cause in skin is important for tightly controlling the release of air pollutants and preventing more serious diseases. This study investigates if such alterations are present in reconstructed human epidermis exposed to coarse air PM. Exposure of reconstructed human epidermis to increasing concentrations (2.2, 8.9, and 17.9 µg/cm2) of standard urban PM over time led to decreased cell viability at 48 hours. The barrier function was shown to be compromised by 24 hours of exposure to high doses (17.9 µg/cm2). Morphological alterations included cytoplasm vacuolization and partial loss of epidermal stratification. Cytokeratin 10, involucrin, loricrin, and filaggrin protein levels were significantly decreased. We confirmed an inflammatory process by IL-1α release and found a significant increase in AQP3 expression. We also demonstrated changes in NOTCH1 and AhR expression of epidermis treated with coarse air PM. The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cysteine altered NOTCH1 expression, suggesting that this is a redox-dependent process. These results demonstrate that coarse air PM induces dose-dependent inflammatory response and alterations in protein markers of differentiation and water transport in the epidermis that could ultimately compromise the structural integrity of the skin, promoting or exacerbating various skin diseases.

Advances in dermatology using DNA aptamer "Aptamin C" innovation: Oxidative stress prevention and effect maximization of vitamin C through antioxidation.

BACKGROUND: Vitamin C (also known as L-ascorbic acid) plays a critical role in reactive oxygen species (ROS) reduction and cell regeneration by protecting cell from oxidative stress. Although vitamin C is widely used in cosmetic and therapeutic markets, there is considerable evidence that vitamin C easily undergoes oxidation by air, pH, temperature, and UV light upon storage. This deficiency of vitamin C decreases its potency as an antioxidant and reduces the shelf-life of products containing vitamin C as its ingredient. To overcome the deficiency of vitamin C, we have developed Aptamin C, an innovative DNA aptamer maximizing the antioxidant efficacy of vitamin C by binding to the reduced form of vitamin C and delaying its oxidation. METHODS: Binding of Aptamin C with vitamin C was determined using ITC analysis. ITC experiment was performed 0.2 mmol/L vitamin C that was injected 25 times in 2 µL aliquots into the 1.8 mL sample cell containing the Aptamin C at a concentration of 0.02 mmol/L. The data were fitted to a one-site binding isotherm using with origin program for ITC v.5.0. RESULTS: To investigate the effect of Aptamin C and vitamin C complex in human skins, both in vitro and clinical tests were performed. We observed that the complex of Aptamin C and vitamin C was significantly effective in wrinkle improvement, whitening effect, and hydration increase. In the clinical test, subjects treated with the complex showed dramatic improvement in skin irritation and itching. No adverse reaction was presented by Aptamin C complex in the test. CONCLUSION: Taken together, these results showed that Aptamin C, an innovative novel compound, should potentially be served as a key cosmeceutical ingredient for a range of skin conditions.

Peptides Derived from the Tight Junction Protein CLDN1 Disrupt the Skin Barrier and Promote Responsiveness to an Epicutaneous Vaccine.

Keratinocytes express many pattern recognition receptors that enhance the skin's adaptive immune response to epicutaneous antigens. We have shown that these pattern recognition receptors are expressed below tight junctions (TJ), strongly implicating TJ disruption as a critical step in antigen responsiveness. To disrupt TJs, we designed peptides inspired by the first extracellular loop of the TJ transmembrane protein CLDN1. These peptides transiently disrupted TJs in the human lung epithelial cell line 16HBE and delayed TJ formation in primary human keratinocytes. Building on these observations, we tested whether vaccinating mice with an epicutaneous influenza patch containing TJ-disrupting peptides was an effective strategy to elicit an immunogenic response. Application of a TJ-disrupting peptide patch resulted in barrier disruption as measured by increased transepithelial water loss. We observed a significant increase in antigen-specific antibodies when we applied patches with TJ-disrupting peptide plus antigen (influenza hemagglutinin) in either a patch-prime or a patch-boost model. Collectively, these observations demonstrate that our designed peptides perturb TJs in human lung as well as human and murine skin epithelium, enabling epicutaneous vaccine delivery. We anticipate that this approach could obviate currently used needle-based vaccination methods that require administration by health care workers and biohazard waste removal.

Evaluation of moisturizing and irritation potential of sacha inchi oil.

OBJECTIVE: The moisturizing and irritation effects of sacha inchi oil were evaluated. STUDY DESIGN: The moisturizing effect on the skin was clinically assessed using a regression study design. Sacha inchi oil or olive oil (benchmark) was applied on the left or right lower leg of the subjects for 14 days followed by application discontinuation for 2 days. The TEWL, skin moisture content and dryness appearance were observed. METHODS: The fatty acid composition and characteristics of cold-pressed sacha inchi seed oil were determined. Skin tissues cultured ex vivo were used to assess primary irritation induced by the oil by examining keratin 1 expression and TNF-α and IL-1α release from the oil-applied tissues. RESULTS: The sacha inchi oil contained 42.3% linolenic acid and 39.5% linoleic acid. This oil's saponification, iodine, acid and peroxide values were 168.58 ± 1.55 mg KOH/g, 203.00 ± 0.04 g I2 /100 g, 1.68 ± 0.03 mg KOH/g, and 1.95 ± 0.26 mEq peroxide/kg, respectively. Compared with nontreated skin tissues, induced secretion of TNF-α and IL-1α and disruption of keratin 1 integrity in the stratum corneum layer were not found in the sacha inchi oil-treated tissues. In a clinical study with 13 volunteers, the improvement in moisture content and skin dryness appearance at the sacha inchi oil-applied site was comparable with that observed at the olive oil-applied site. CONCLUSIONS: The sacha inchi oil was mild to the skin and benefited dry skin.

Barrier damaging effects of n-propanol in occlusion-modified tandem repeated irritation test: Modulation by exposure factors and atopic skin disease.

BACKGROUND: Recent studies provide evidence for significant and previously underestimated barrier damaging effects of repeated exposure to 60% n-propanol in healthy skin in vivo. OBJECTIVES: To investigate further the cumulative effects of a range of n-propanol concentrations relevant at the workplace in healthy and atopic dermatitis (AD) individuals, and study the modulation of the outcomes by co-exposure and host-related factors. METHODS: Healthy adult and AD volunteers were exposed to n-propanol concentrations from 30% to 75% in occlusion-modified tandem repeated irritation test with measurements of erythema, transepidermal water loss, capacitance, and the natural moisturizing factor (NMF) levels at baseline and after 96 hours. RESULTS: n-Propanol exerted significant barrier damaging effects even at the lowest concentration in both groups. Exposure to all n-propanol concentrations significantly reduced the NMF levels. Preceding low-grade trauma by occlusion/water exposure reduced the skin irritation threshold in both groups. The differences in the severity of the barrier function impairment after exposure to the same concentrations under the same conditions between the AD and control groups were significant. CONCLUSIONS: The negative effects of cumulative exposure to n-propanol in healthy and atopic skin shown in the study suggest the need for critical re-evaluation of its irritant properties in vivo.

Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers.

Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.

Topical application of highly concentrated water-in-oil emulsions: Physiological skin parameters and skin penetration in vivo - A pilot study.

Important aspects in the development of new dermal drug delivery systems are the formulations' physicochemical properties and stability. Moreover, their influence on skin physiology and their penetration performance in vivo are of crucial interest. We have recently developed novel concentrated water-in-oil emulsions based on a non-ionic silicone surfactant; the present study deals with the effect of these formulations on physiological skin parameters of healthy volunteers after repeated application. Variations in skin condition and barrier integrity were investigated using classical biophysical and spectroscopic techniques. After four weeks of continuous treatment, no signs of skin irritation could be observed. Both tested emulsions had a positive effect on skin properties despite their relatively high water content and low lipid content. In vivo tape stripping studies revealed penetrated amounts of the incorporated model drug fluorescein sodium of almost 50% of the applied dose, with a superior performance of emulsions with isopropyl myristate when compared to liquid paraffin. In summary, our study confirmed the suitability of the developed W/O emulsions for pharmaceutic and cosmetic applications.

Integrating tacrolimus into eutectic oil-based microemulsion for atopic dermatitis: simultaneously enhancing percutaneous delivery and treatment efficacy with relieving side effects.

Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs. Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506. Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1-chloro-2, 4-dinitrobenzene (DNCB)-induced murine AD. Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application. Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence. Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537).