Effect of a Tranexamic Acid, Kojic Acid, and Niacinamide Containing Serum on Facial Dyschromia: A Clinical Evaluation

Background: Stubborn dyschromia such as melasma and post-inflammatory hyperpigmentation (PIH) are leading causes for cosmetic consultation. Topical treatment is challenging, using a range of modalities, to stop, hinder, and/or prevent steps in the pigment production process. Tranexamic acid (TXA), a potent plasmin inhibitor, is proposed to control pigmentation by inhibiting the release of inflammatory mediators involved in triggering melanogenesis. TXA has been recently introduced as a topical therapy aimed at reducing pigmentation in melasma. Methods: In a 12-week clinical study, a novel, topical facial serum containing 3% TXA, 1% kojic acid, and 5% niacinamide was evaluated for its effectiveness in treating melasma, PIH, and hyperpigmentation in Brazilian female subjects with Fitzpatrick skin types I-IV. Efficacy evaluations were performed at pre-treatment baseline, weeks 2, 4, 8, and 12, and included expert clinical grading, bio-instrumental measurements, and self-assessment questionnaires. Cutaneous tolerability was also evaluated by assessing subjective and objective irritation of the treatment area. Results: A significant improvement in the appearance of PIH, hyperpigmentation, melasma, skin texture, and skin tone homogeneity was observed beginning at week 2 and continued through week 12. Melanin index, as measured by Mexameter®, demonstrated a significant decrease by week 12 as compared to both pre-treatment baseline and control. Conclusions: The findings suggest that the test product is an effective and well-tolerated treatment option for addressing hyperpigmentary conditions, including melasma. Additional in vitro data suggests that TXA may act by mediating the inhibition of PGE2-stimulated human epidermal melanocytes. J Drugs Dermatol. 2019;18(5):454-459.

Soft, stretchable, epidermal sensor with integrated electronics and photochemistry for measuring personal UV exposures.

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application.

Clinical Evaluation of a Multi-Modal Facial Serum That Addresses Hyaluronic Acid Levels in Skin.

BACKGROUND: Hyaluronic acid (HA), the major glycosaminoglycan present in the human skin, is a key contributor to water retention and mechanical support in skin. The level, size, and functionality of cutaneous HA are known to diminish with age. Topical treatments designed to increase the HA content of skin have been met with limited success. The purpose of this study was to evaluate the tolerance and efficacy of a multi-modal facial serum containing HA, Proxylane (C-Xyloside), purple rice extract, and dipotassium glycyrrhizate in addressing HA levels in skin. METHODS: A 12-week, single center, clinical study was conducted on 59 women with mild to moderate photodamage. Clinical grading to assess the efficacy and tolerability was conducted on the face at baseline and at weeks 4, 8, and 12. Bioinstrumentation measurements were taken, including corneometer, tewameter, ultrasound, and standardized digital imaging. A randomized subset of 20 subjects from the study population had 3 mm punch biopsies collected for quantitative RT-PCR analysis from 2 sites on the face at baseline and week 12. Additionally, a 4-week, single center, clinical study was conducted on the photodamaged forearms of 12 subjects. At both baseline and week 4, a 4 mm punch biopsy was obtained from the subjects' randomized forearms. Biopsy samples were subjected to immunohistochemical staining and analysis of HA content. RESULTS: Statistically-significant improvements in all facial skin attributes (weeks 4, 8, and 12), stratum corneum hydration (week 12), and transepidermal water loss (week 12) were observed. Tolerability was excellent, with no increases in irritation parameters noted. A significant increase of HA content in skin after 4 weeks of treatment was observed. By PCR analysis, there was a significant increase in hyaluronan synthase 2, as well as a significant increase in collagen type 1a1 after 12 weeks of application. CONCLUSION: The findings suggest that this novel topical facial serum is capable of stimulating HA and skin extracellular matrix components, as well as improving skin hydration and skin quality in women with mild to moderate photodamage.

J Drugs Dermatol. 2017;16(9):884-890.

Multimodal epidermal devices for hydration monitoring.

Precise, quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skin-based pathologies, and regulating external appearance. Here we introduce multimodal sensors with important capabilities in this context, rendered in soft, ultrathin, 'skin-like' formats with numerous advantages over alternative technologies, including the ability to establish intimate, conformal contact without applied pressure, and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin. Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature, thermal conductivity, thermal diffusivity, volumetric heat capacity, and electrical impedance using simple analysis algorithms. Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat.

Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate.

Thermal transport characteristics of human skin measured in vivo using ultrathin conformal arrays of thermal sensors and actuators.

Measurements of the thermal transport properties of the skin can reveal changes in physical and chemical states of relevance to dermatological health, skin structure and activity, thermoregulation and other aspects of human physiology. Existing methods for in vivo evaluations demand complex systems for laser heating and infrared thermography, or they require rigid, invasive probes; neither can apply to arbitrary regions of the body, offers modes for rapid spatial mapping, or enables continuous monitoring outside of laboratory settings. Here we describe human clinical studies using mechanically soft arrays of thermal actuators and sensors that laminate onto the skin to provide rapid, quantitative in vivo determination of both the thermal conductivity and thermal diffusivity, in a completely non-invasive manner. Comprehensive analysis of measurements on six different body locations of each of twenty-five human subjects reveal systematic variations and directional anisotropies in the characteristics, with correlations to the thicknesses of the epidermis (EP) and stratum corneum (SC) determined by optical coherence tomography, and to the water content assessed by electrical impedance based measurements. Multivariate statistical analysis establishes four distinct locations across the body that exhibit different physical properties: heel, cheek, palm, and wrist/volar forearm/dorsal forearm. The data also demonstrate that thermal transport correlates negatively with SC and EP thickness and positively with water content, with a strength of correlation that varies from region to region, e.g., stronger in the palmar than in the follicular regions.

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

PURPOSE: This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. EXPERIMENTAL DESIGN: Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. RESULTS: The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. CONCLUSION: Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

Antioxidants and the skin: understanding formulation and efficacy.

Antioxidants are molecules capable of inhibiting the oxidation of other molecules. Although oxidation reactions are essential for life, they can also be damaging. All living organisms maintain complex systems of multiple types of antioxidants to protect their cells from oxidative damage. Antioxidants can also act as pro-oxidants, under certain circumstances. The efficacy and benefit of an antioxidant is, therefore, very much dependent on the delivery of the antioxidant to the organism. Topically applied antioxidants constitute an important group of pharmacologically active agents capable of preventing the occurrence and reducing the severity of UV-induced skin damage and skin aging. Antioxidants protect skin cells against the damaging effects of reactive oxygen species (ROS), such as singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals, and peroxynitrite. ROS induced oxidative stress in the skin has been linked to cancer, aging, inflammation, and photodamage. This review focuses on antioxidants used in the cosmetic industry for protection of skin, formulation methods used to enhance their efficacy, and methods used to test the efficacy of antioxidants in topical formulations.