The heterogeneity and complexity of skin surface lipids in human skin health and disease.

The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters. The balance of these skin surface lipids in terms of their relative abundance, composition, molecular organisation and dynamics, and their intricate interactions play a crucial role in the maintenance of healthy skin. For that reason, even minuscule alterations in skin surface lipid properties or overall lipid profile have been implicated in the aetiology of many common skin diseases including atopic dermatitis, psoriasis, xerosis, ichthyosis and acne. Novel lipid-based interventions aimed at correcting the skin surface lipid abnormalities have the potential to repair skin barrier integrity and the symptoms associated with such skin diseases, even though the exact mechanisms of lipid restoration remain elusive.

Autophagy is the key to making chronic wounds acute in skin wound healing.

As a highly regulated and dynamically balanced intracellular degradation mechanism, macroautophagy/autophagy plays an essential housekeeping role in different successive stages of skin wound healing; from the homeostasis and inflammatory stages to the proliferative and remodeling stages. Under both progressive and defective skin wound healing conditions, autophagy operates at different levels with a precise extent of activity, at the interface of inflammation, stress signaling and cell metabolism through a complex spatiotemporal cascade of molecular and cellular events. Depending on the wound healing conditions autophagic activity is fine-tuned and differentially modulated at each stage of skin wound healing in order to cope with stage-specific requirements. Here, we postulate that under favorable conditions autophagy may act as the key modulator of skin wound healing by making chronic wounds acute. Enhancing autophagy through the topical application of pro-autophagy biologics in an appropriate hydrating vehicle/moisturizing base such as hydrogels, onto a chronic skin wound may provide moisture and immune modulation, thus contributing to rapid and efficient skin wound healing. A moist environment is more conducive to skin wound healing as it helps to not only accelerate cell proliferation and migration, and extracellular matrix reorganization, but also promotes autophagy and reduces the incidence of inflammation.Abbreviation: AKT: AKT serine/threonine protein kinase; ECM: extracellular matrix; FN1: fibronectin 1; LAM: laminin; MMPs: matrix metallopeptidases; MMP2: matrix metallopeptidase 2; MRSA: methicillin-resistant Staphylococcus aureus; MTOR: mechanistic target of rapamycin kinase; PI3K: phosphoinositide 3-kinase; TNF/TNF-α: tumor necrosis factor.

Emerging Trends in the Use of Topical Antifungal-Corticosteroid Combinations.

A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin infections. Their many benefits, owing to their specific mechanism of action, include their ability to target the site of infection, enhance treatment efficacy and reduce the risk of systemic side effects. Their proven efficacy, and positioning in the treatment of fungal skin infections, is enhanced by high patient compliance, especially when appropriate vehicles such as creams, ointments and gels are used. However, inflammation as a result of fungal infection can often impede treatment, especially when combined with pruritus (itch), an unpleasant sensation that elicits an urge to scratch. The scratching that occurs in response to pruritus frequently accelerates skin damage, ultimately aggravating and spreading the fungal infection. To help overcome this issue, a topical antifungal-corticosteroid combination consisting of miconazole or terbinafine and corticosteroids of varying potencies should be used. Due to their inherent benefits, these topical antifungal-corticosteroid combinations can concomitantly and competently attenuate inflammation, relieve pruritus and treat fungal infection.

Skin Cleansing without or with Compromise: Soaps and Syndets.

Products designed to cleanse the skin commonly do so through surfactant action, which leads to the lowering of the surface tension of the skin to facilitate the removal of dirt from its surface. Skin cleansers generally come in one of two types: soap-based and synthetic detergents, or syndets. While the latter can effectively maintain the native skin structure, function and integrity, the former tends to negatively affect the skin by causing barrier disruption, lipid dissolution and pH alteration. Despite this, soap is still often preferred, possibly due to the negative connotations around anything that is not perceived as 'natural'. It is, therefore, important that the science behind cleansers, especially those designed for the maintenance of healthy skin and the management of common skin conditions such as eczema, be understood by both formulators and end-users. Here, we carefully weigh the advantages and disadvantages of the different types of surfactant-the key ingredient(s) in skin cleansers-and provide insight into surfactants' physicochemical properties, biological activity and potential effects. Fine-tuning of the complex characteristics of surfactants can successfully lead to an 'optimal' skin cleanser that can simultaneously be milder in nature, highly effective and beneficial, and offer minimal skin interference and environmental impact.

Vehicles for Drug Delivery and Cosmetic Moisturizers: Review and Comparison.

Many dermatological conditions, such as eczema and psoriasis, are treated with topical therapeutic products. Instead of applying the active drug directly onto the skin, it is combined with a vehicle to aid in its delivery across the stratum corneum (SC) and into deeper regions of the skin, namely the epidermis and dermis. Absorption into the systemic circulation is minimized. Topical vehicles are also used as cosmetic moisturizers (often termed emollient therapy) to ameliorate dry skin, which is a cornerstone of the management of various dermatological conditions, including xerosis, eczema, psoriasis, and aging. The most common topical vehicles include ointments, creams, gels, and lotions, among others. It is crucial that topical vehicles are chosen based upon the size and properties (wet/dry, mucous/non-mucous, healthy/diseased) of the skin to be treated in order to optimize application and contact of the product with the skin, as this can have profound impacts on potency, efficacy, and patient compliance. This review examines common topical vehicles used for drug delivery and cosmetic moisturizers, including their formulation, advantages and disadvantages, and effects on the skin. The unique rules imposed by governing regulatory bodies in Australia and around the world, in terms of topical product claims, are also briefly examined.

Recruitment of adults with moderate eczema for a randomised trial: Comparison of traditional versus modern methods.

BACKGROUND: Clinical trial recruitment is challenging for investigators who often overestimate the pool of qualified, willing subjects. Moreover, there is a paucity of literature, particularly in dermatology, regarding recruitment and the comparative success of advertising strategies. METHODS: Both 'traditional' (physician referral, newspaper and radio advertisements, letterbox drops, posters/flyers, word-of-mouth) and 'modern' (patient recruitment services, social media, Google advertisements, websites, email) recruitment methods were used to enrol 100 patients (>18 years) diagnosed with moderate eczema for a randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of a topical eczema treatment over 4 weeks. The relationships between recruitment method and patient age, sex, race, study completion and costs were analysed. RESULTS: The majority of patients recruited were young, with millennials and Gen Z comprising 77% of the study population. Both traditional and modern recruitment methods were equally successful in recruiting younger patients, with older patients predominately recruited by traditional methods. Eighty per cent more men were recruited by traditional compared to modern methods, whilst 67% more women than men were recruited by modern methods. Recruitment method neither appeared to be influenced by race, nor did it effect whether patients completed the study. Costs per enrolment were similar for both methods. CONCLUSIONS: This study shows that despite the high proportion of young patients and the rising popularity of social media and increased internet use, a combination of both traditional and modern recruitment methods was required to successfully meet the trial enrolment target of 100 adult patients with moderate eczema.

A daily regimen of a ceramide-dominant moisturizing cream and cleanser restores the skin permeability barrier in adults with moderate eczema: A randomized trial.

The dysfunctional skin barrier in eczema patients may be attributed to decreased levels of ceramides in the stratum corneum. The aim of this study was to determine whether a two-part system consisting of a ceramide-dominant physiological lipid-based moisturizing cream and cleanser could ameliorate the signs and symptoms of moderate eczema in adults over 28 days compared to placebo. Assessments were conducted at baseline and every 7 days thereafter. Eczema area severity index score decreased significantly across all time points in both groups compared to baseline (P < .0001), however, this decrease was not significant between groups at day 28 (P = .7804). In contrast, transepidermal water loss and skin hydration significantly improved over time in the active group, while it either stayed the same or worsened in the placebo group (P = .0342 and P < .0001, respectively). There was no difference in the use of mometasone furoate as rescue medication over time between groups (P = .1579). Dermatology life quality index scores improved significantly in both groups (P < .0001), with no difference between groups (P = .5256). However, patient satisfaction was greater in the active compared to the placebo group for several parameters including relief of itch, dry skin, skin softness and smoothness (all P < .05). No patients withdrew from the study due to adverse events (AEs) and there were no serious AEs. The ceramide-dominant moisturizing cream and cleanser safely restores skin permeability and improves the signs and symptoms of eczema in adults.

Emollient formulations containing antiseptics reduce effectively the level of Staphylococcus aureus on skin.

BACKGROUND: Increased skin colonization by Staphylococcus aureus is associated with atopic eczema (AE) severity. Reduction of S. aureus levels on the skin results in an improvement in the clinical condition. METHODS: The antimicrobial activity of topical products including a bath oil, cream, and wash combining antiseptics and emollients (A+E) was compared to products containing emollients only. The preference of patients with AE for A+E cream or emollient only cream to relieve symptoms of itching, erythema, and inflammation when applied three times daily for 10 days is evaluated. Repeat insult patch testing of the products is also conducted. RESULTS: A significant reduction in microbial counts was found following use of A+E bath oil (4.09±0.32 vs 6.20±0.24 log10 cfu/mL S. aureus, P<0.001), A+E cream (5.50±0.63 vs 5.94±0.72 log10 cfu/foot S. aureus, P=0.002), and A+E wash (2.71±0.48 vs 3.57±0.31 log10 cfu/mL Escherichia coli, P<0.001) compared to the emollient only products. The A+E cream was preferred to the emollient only cream (P=0.004) by patients with AE. All three tested formulations were found to be non-irritating and non-sensitizing to the skin. CONCLUSION: The bath oil, cream, and wash containing antiseptics and emollients decrease the level of bacteria on the skin, including S. aureus, compared to emollient only products. Patients with AE preferred the A+E cream compared to the emollient only cream to relieve symptoms of itching, erythema, and inflammation. The choice of formulation allows clinicians and patients to choose a suitable product for the short-term treatment of eczema flare-ups caused by bacterial infections.

Breaking the Itch-Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis.

Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be hugely debilitating for the sufferer, damaging in terms of both the monetary cost of treatment and its socioeconomic effects, and few treatment options exist that can adequately control it. Corticosteroids remain the first line treatment strategy for atopic dermatitis, but due to the risks associated with long-term use of corticosteroids, and the drawbacks of other topical options such as topical calcineurin inhibitors and capsaicin, topical options for itch management that are efficacious and can be used indefinitely are needed. In this review, we detail the pathophysiology of chronic pruritus, its key features, and the disease most commonly associated with it. We also assess the role of the skin and its components in maintaining a healthy barrier function, thus reducing dryness and the itch sensation. Lastly, we briefly detail examples of topical options for the management of chronic pruritus that can be used indefinitely, overcoming the risk associated with long-term use of corticosteroids.

Use of formulations for sensitive skin improves the visible signs of aging, including wrinkle size and elasticity.

Background: Sensitive skin affects an increasingly large proportion of the population and is less tolerant to frequent and prolonged use of cosmetics. This study investigates the antiaging effects of a skin care system developed for use on sensitive skin. Methods: A total of 30 healthy Caucasian females, aged 32-72, were enrolled in this double-blind randomized placebo-controlled split-face study. A routine consisting of twice daily topical applications of the test cleanser and test moisturizer or placebo or positive control products was followed for 28 days, with parameters measured at baseline and at 7-day intervals. Objective skin assessments for hydration, transepidermal water loss (TEWL), skin surface topography, elasticity and safety assessment were conducted. Results: Wrinkle surface, length and depth significantly improved by 34.8±4.7% (P<0.001), 19.0±3.2% (P<0.05) and 24.3±3.5% (P<0.05), respectively, after 28 days of skin care treatment with the test cleanser and test moisturizer. R2 (gross elasticity), R5 (net elasticity) and R7 (biological elasticity) significantly increased by 32.8±6.5% (P<0.001), 47.3±8.6% (P<0.001) and 50.6±5.1% (P<0.001), respectively, while R6 (viscoelastic portion) significantly decreased by 33.4±4.6% (P<0.001) after 28 days. Skin hydration was also found to increase significantly after 28 days by 42.2±8.5% (P<0.01), but there was no change in TEWL. No adverse events were reported. Conclusions: A novel skin care routine developed for use on sensitive skin significantly improves the signs of aging including hydration, wrinkle size and elasticity without significant adverse effects.

Skin hydration is significantly increased by a cream formulated to mimic the skin's own natural moisturizing systems.

BACKGROUND: Moisturizers are topical products designed to improve and maintain the skin barrier function and to help prevent dry skin. MATERIALS AND METHODS: A new moisturizer (Ceramide cream) was formulated containing ingredients which mimic the skin's own natural moisturizing systems. Corneometry was performed at baseline, 2, 4, 6 and 24 hours following a single application of Ceramide cream to healthy skin, and compared to three reference moisturizers available over-the-counter, and placebo. Transepidermal water loss (TEWL) was also measured following a single application of Ceramide cream compared to baseline, and its safety was assessed by repeat insult patch test, ophthalmologist and pediatric testing. RESULTS: A single topical application of either the Ceramide cream or the three reference moisturizers resulted in a significant increase in skin hydration over time (P<0.001). The placebo cream did not significantly increase skin hydration at any time point. At 24 hours post-application, skin hydration measured for Ceramide cream was significantly greater (P<0.05) than that measured for all three of the reference moisturizers tested. Ceramide cream was also found to significantly decrease TEWL (P<0.001) over 24 hours, and was shown to be non-sensitizing to the skin of both adults and children and non-irritating to the skin, eyes and related eye area. CONCLUSION: Ceramide cream increases skin hydration and improves barrier function which may make it suitable for use on dry skin.

Hydrogels for Atopic Dermatitis and Wound Management: A Superior Drug Delivery Vehicle.

Wound management, in addition to presenting a significant burden to patients and their families, also contributes significantly to a country’s healthcare costs. Treatment strategies are numerous, but in most cases not ideal. Hydrogels, three-dimensional polymeric materials that can withstand a great degree of swelling without losing structural integrity, are drawing great attention for their use as topical wound management solutions in the form of films and as vehicles for drug delivery, due to their unique properties of high water content, biocompatibility, and flexibility. Hydrogels, both naturally and synthetically derived, can be tuned to respond to specific stimuli such as pH, temperature and light and they are ideally suited as drug delivery vehicles. Here we provide a brief overview of the history and characteristics of hydrogels, assess their uses in wound management and drug delivery, and compare them with other types of common drug delivery vehicle.

Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids.

Derivatives of hydrocortisone, such as mometasone furoate, a (2') furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.

Water-soluble benzoheterocycle triosmium clusters as potential inhibitors of telomerase enzyme.

We have studied the ability of several bioorganometallic clusters [(mu-H)Os(3)(CO)(9)(L)(mu(3)-eta(2)-(Q-H))], where L = [P(C(6)H(4)SO(3)Na)(3)] or [P(OCH(2)CH(2)NMe(3)I)(3)], and Q = quinoline, 3-aminoquinoline, quinoxaline or phenanthridine, of inhibiting telomerase, a crucial enzyme for cancer progression. In general, quinolines have shown interesting biological properties, especially in inhibiting enzymes. For example, the 2,3,7-trichloro-5-nitroquinoxaline (TNQX) exhibited strong anti-telomerase activity in vitro. Among the quinoline-clusters under study, only the negatively charged ones (by virtue of the sulfonated phosphines) exhibited good anti-telomerasic activity on semi-purified enzyme in a cell-free assay, while they were ineffective in vitro on Taq, a different DNA-polymerase. On the contrary, the treatment of breast cancer MCF-7 cell line did not evidence any activity of these clusters, suggesting a low aptitude for crossing cell membrane. Furthermore, all clusters exhibited non-specific, acute cytotoxicy, probably due to accumulation on cell membranes by virtue of their amphiphilic character. A detailed study of Os uptake and accumulation in MCF-7 cells supported this hypothesis.