Spherical Nucleic Acids for Topical Treatment of Hyperpigmentation.

Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

Algae Metabolites in Cosmeceutical: An Overview of Current Applications and Challenges.

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals' larger molecular size. The cosmetic industry uses the term "cosmeceutical", referring to a cosmetic product that is claimed to have medicinal or drug-like benefits. Marine algae have gained tremendous attention in cosmeceuticals. They are one of the richest marine resources considered safe and possessed negligible cytotoxicity effects on humans. Marine algae are rich in bioactive substances that have shown to exhibit strong benefits to the skin, particularly in overcoming rashes, pigmentation, aging, and cancer. The current review provides a detailed survey of the literature on cosmeceutical potentials and applications of algae as skin whitening, anti-aging, anticancer, antioxidant, anti-inflammation, and antimicrobial agents. The biological functions of algae and the underlying mechanisms of all these activities are included in this review. In addition, the challenges of using algae in cosmeceutical applications, such as the effectiveness of different extraction methods and processing, quality assurance, and regulations concerning extracts of algae in this sector were also discussed.

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Formulation and clinical evaluation of the standardized Litchi chinensis extract for skin hyperpigmentation and aging treatments.

INTRODUCTION: The standardized litchi extract had been revealed on phytochemical actives, in vitro and cellular activities against aging and darkening of skin. However, a formulation containing the extract has never been developed as per clinical evaluated. MATERIALS AND METHODS: The litchi serum was developed, safety and efficacy were clinically evaluated in human volunteers. The stable and none irritated 0.05 and 0.1% litchi serums were randomized-single blind placebo control clinical applied on the inner forearm of 29 volunteers for a consecutive 112 days and monitored by Mexameter® MX18, Cutometer® MPA 580 and Visioscan® VC 98. RESULTS: Skin lightening efficacy of the 0.1% and 0.05% litchi serum was significantly (P<0.001 and P<0.05) higher than the placebo. Skin elasticity and wrinkle reduction was significantly (P<0.05 and P<0.005) achieved by the 0.1% litchi serum. The efficacy of litchi serums was confirmed by a split-face, randomized, single-blind controlled that the 0.1% litchi serum was significantly (P<0.05) better than the 0.05% one of all examined parameters. CONCLUSION: Safety and efficacy of litchi extract are clinically confirmed for hyperpigmentation and aging of skin treatments.

Melasma: Updates and perspectives.

Management of melasma is highly challenging due to inconsistent treatment results and frequent relapses. However, recent studies revealed that melasma may not only be a disease of melanocytes, but also a photoaging skin disorder. Herein, we attempt to validate that melasma is indeed a photoaging disorder by presenting the histopathologic findings of melasma: solar elastosis, altered basement membrane, increased vascularization and increased mast cell count. We also provide some therapeutic implications based on these findings and a discussion on the latest updates and perspectives regarding treatment.

Minimal erythema dose, minimal persistent pigment dose which model for whitening products evaluation is better?

BACKGROUND/AIMS: How to select a suitable method in whitening products evaluation is still under discussion. Here, we compared two different artificial pigmentation models and explored an ideal UV dosage for skin whitening products evaluation model establishment. METHODS: Thirty five healthy volunteers with type IV human skin were recruited and the skin minimal erythema dose (MEDs) and minimal persistent pigment dose (MPPDs) were measured. All volunteers were simultaneously exposed to six increasing doses of radiations from different ultraviolet sources on lower back bilateral flattening area: 95% UVA/5% UVB with the radiating doses of 0.75, 0.94, 1.17, 1.46, 1.83, 2.29 MEDs was used on the left side; meanwhile 99% UVA/1% UVB with radiating doses of 6.0, 7.5, 9.4, 11.7, 14.6, 18.3 MPPDs were used on the right side. Observations and pigmentation measurements were carried out before and after UV radiation for 24 weeks. RESULT: 1.83 MED and 2.29 MED induced medium depth pigmentation by 95% UVA/5% UVB irradiation. 1.83 MED dose causing minimal photo-damage on skin was selected as the most suitable dose. With 99% UVA/1% UVB irradiation, 9.4 MPPD and 11.7 MPPD induced medium depth pigmentation. 9.4 MPPD dose causing minimal photo-damage on skin was selected. CONCLUSION: These findings potentiate advanced understanding of UV model establishment and selection for skin whitening products evaluation as related to dermatopharmacology and dermatotoxicology.

Detection of hydroquinone by Raman spectroscopy in patients with melasma before and after treatment.

BACKGROUND: Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans. MATERIAL AND METHODS: In this work, Raman spectroscopy was used to observe the presence of hydroquinone in the skin of 18 patients who have been under treatment for melasma. RESULTS: A significant increase in the Raman signal was observed in the six bands associated with hydroquinone after melasma treatment. CONCLUSION: The authors believe that monitoring the presence of hydroquinone may be useful for an optimal personalized treatment of melasma and to provide the specialist a support tool to control the administration of this type of bleaching agents.

Hyperpigmentation Disorders in Hispanic Population in the United States

The Hispanic population is the third largest growing group in the United States and is projected to increase to 119 million by 2060. Skin of color populations including Hispanics are more susceptible to a variety of pigmentary disorders including melasma and post-inflammatory hyperpigmentation (PIH). Most previous treatment options for these disorders remain unsatisfactory. Current treatment options include topical therapies using skin lightening/bleaching agents, chemical peels, and physical therapies such as microdermabrasion, microneedling, radiofrequency, and lasers. Combination therapies using skin lighting agents, peels, and physical means are also commonly used. New trends include protection and prevention using sunscreens, physical blockers, and the use of new and effective anti-oxidants and anti-inflammatory agents. The choice of therapeutic agents involves assessment of the risk-benefit profile of each individual. As the pathophysiology of melasma and PIH are being intensely investigated and studied, the treatment options are also expanding. In this review, the current therapeutic options are summarized and new and emerging treatment options for PIH and melasma are discussed. J Drugs Dermatol. 2019;18(3 Suppl):s112-114.

Hyperpigmentation Disorders in Hispanic Population in the United States

The Hispanic population is the third largest growing group in the United States and is projected to increase to 119 million by 2060. Skin of color populations including Hispanics are more susceptible to a variety of pigmentary disorders including melasma and post-inflammatory hyperpigmentation (PIH). Most previous treatment options for these disorders remain unsatisfactory. Current treatment options include topical therapies using skin lightening/bleaching agents, chemical peels, and physical therapies such as microdermabrasion, microneedling, radiofrequency, and lasers. Combination therapies using skin lighting agents, peels, and physical means are also commonly used. New trends include protection and prevention using sunscreens, physical blockers, and the use of new and effective anti-oxidants and anti-inflammatory agents. The choice of therapeutic agents involves assessment of the risk-benefit profile of each individual. As the pathophysiology of melasma and PIH are being intensely investigated and studied, the treatment options are also expanding. In this review, the current therapeutic options are summarized and new and emerging treatment options for PIH and melasma are discussed. J Drugs Dermatol. 2019;18(3 Suppl):s112-114.

Azelaic acid-loaded nanoemulsion with hyaluronic acid - a new strategy to treat hyperpigmentary skin disorders.

OBJECTIVE: To develop an azelaic acid (AzA)-loaded nanoemulsion with hyaluronic acid (HA) as a double targeting strategy to increase drug retention and tyrosinase inhibition activity. SIGNIFICANCE: Dermic melasma is a recalcitrant disease. Therefore, the development of new technologies that allow a deeper penetration in the skin while enhancing the efficacy of a safe and well-known dermatological active, like AzA, is a very promising alternative to improve the treatment of this disease. METHODS: An oil-in-water nanoemulsion was developed and characterized according to its droplet size distribution, zeta potential, pH value, drug content, encapsulation efficiency, spectroscopic characteristics, morphology, and stability. In vitro mushroom tyrosinase inhibition assay, cytotoxicity, and permeation studies were performed. A descriptive sensory evaluation was also carried out. RESULTS: Drug content was 10 mg/ml, particle size 419 ± 23 nm with monomodal distribution, encapsulation efficiency was 84.65%, zeta potential -10.9 ± 0.44 mV and pH 5.01 ± 0.01. The nanoemulsion was stable for 30 days (30 °C/65% RH). The nanoemulsion decreased tyrosinase activity and permeated through the skin, reaching viable epidermis and dermis and did not show signs of cytotoxicity. Sensory evaluation profile showed a higher spreadability with lesser whitening residue. CONCLUSION: The nanoemulsion presented characteristics within the nanoscale and reached the deeper layers of the skin while improving in vitro tyrosinase inhibition; hence, it could be a promising treatment to dermic melasma.

YouTube as a source of information on skin bleaching: a content analysis.

BACKGROUND: Skin bleaching is a common, yet potentially harmful body modification practice. AIM: To describe the characteristics of the most widely viewed YouTube™ videos related to skin bleaching. METHODS: The search term 'skin bleaching' was used to identify the 100 most popular English-language YouTube videos relating to the topic. Both descriptive and specific information were noted. RESULTS: Among the 100 manually coded skin-bleaching YouTube videos in English, there were 21 consumer-created videos, 45 internet-based news videos, 30 television news videos and 4 professional videos. Excluding the 4 professional videos, we limited our content categorization and regression analysis to 96 videos. Approximately 93% (89/96) of the most widely viewed videos mentioned changing how you look and 74% (71/96) focused on bleaching the whole body. Of the 96 videos, 63 (66%) of videos showed/mentioned a transformation. Only about 14% (13/96) mentioned that skin bleaching is unsafe. The likelihood of a video selling a skin bleaching product was 17 times higher in internet videos compared with consumer videos (OR = 17.00, 95% CI 4.58-63.09, P < 0.001). Consumer-generated videos were about seven times more likely to mention making bleaching products at home compared with internet-based news videos (OR = 6.86, 95% CI 1.77-26.59, P < 0.01). CONCLUSIONS: The most viewed YouTube video on skin bleaching was uploaded by an internet source. Videos made by television sources mentioned more information about skin bleaching being unsafe, while consumer-generated videos focused more on making skin-bleaching products at home.

Double Blind, Placebo Controlled Evaluation of a Novel Skin Lightening Agent.

Melasma remains a troubling problem for physicans and patients alike. It is a chronic irregular, symmetric hyperpigmentation seen most often in women. In this study, a unique combination of ingredients with non-irritating properties was tested for treatment of melasma. In a double blind, placebo controlled, split face trial, 17 patients with melasma were treated on one half of the face, left or right, while the other received placebo control. All patients used sunscreen on both sides. Measurement with a colorimeter (Mexameter) was taken at baseline and after 8 weeks of daily use. The active side showed an objective decrease in hyperpigmentation of 14.60% while the control side showed a decrease of 9.82%. We conclude the product provides a non-irritating effective therapy for melasma.

J Drugs Dermatol. 2018;17(1):113-115.

Approach to Skin Lightening in Patients With Melasma.

I read with interest the informative article by Spencer et al1 that describes the efficacious use as a novel skin lightening agent (LumaPro-C) for the treatment of patients with melasma.

Brightening and Improvement of Facial Skin Quality in Healthy Female Subjects With Moderate Hyperpigmentation or Dark Spots and Moderate Facial Aging

Objective: To evaluate the safety and efficacy of ISDINCEUTICS Melaclear® serum (Barcelona, Spain) on skin brightness, skin quality, and signs of facial aging. Design: This was a single-center, observational, open label, prospective clinical study. Ten healthy females (ages 30-70) with moderate signs of facial aging and moderate photodamage (hyperpigmentation and/or sun spots) were enrolled. Treatment consisted of topical twice-daily application of Melaclear serum, morning and evening, to the face and neck for 12 weeks. Efficacy assessments were conducted at weeks 4, 8, and 12. Standardized photographs, expert investigator grading, tolerability assessments, and subjects reported outcome measures were performed at all visits. Adverse events (AEs) were monitored throughout. Visual assessments of the face and neck included grading for radiance, smoothness, pigmentation, erythema, pore size, skin clarity, skin brightness, skin tone, luminosity, skin complexion, photodamage, hyperpigmentation, wrinkle severity, pigment via the modified Melasma Area and Severity Index (MASI), and overall global aesthetic improvement (GAIS). Safety and tolerability assessments included an evaluation of face and neck for stinging/burning by the subject and dryness, scaling, edema, and erythema by the treating investigator at all study visits. Results: All enrolled subjects completed the study. At the 8 and 12-week follow up visit, there was a statistically significant improvement in the investigator GAIS (1.1 and 1.3, respectively) for the face from baseline. MASI scores were all statistically significantly reduced in the face from week 8 onward relative to baseline. In addition, all skin quality parameters assessed in the face significantly improved from baseline to week 12. Subject global aesthetic improvement scale scores (SGAIS) were also significantly improved at week twelve from baseline (1.8 change) as were skin quality assessments. The average rating for patient satisfaction was 2, or "satisfied" with the overall treatment effectiveness from week 4 onwards. For the neck none of the investigator or subject assessments improved significantly at any time point. No adverse events, tolerability events, or unexpected side effects were observed or reported for any of the subjects. Conclusion: Twice a day treatment of women with moderate facial photoaging and hyperpigmentation with Melaclear serum can significantly improve skin quality, reduce the severity and intensity of hyperpigmentation, and improve signs of photodamage within 12 weeks without any side effects. J Drugs Dermatol. 2018;17(12):1310-1315.

Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention.

Postinflammatory hyperpigmentation (PIH) occurs after various dermatoses, exogenous stimuli, and dermatologic procedures. The clinical course of PIH is chronic and unpredictable, although the probability of resolution of epidermal hyperpigmentation is better than those of dermal hyperpigmentation. PIH can be prevented or alleviated. When it does occur, the underlying inflammatory conditions should be sought and treated as the first step to reduce the progression of inflammation and PIH (which is an inflammatory consequence). If the inflammatory conditions subsides or there is no evidence of inflammation at the time of diagnosis, the treatments of PIH should be considered as the next step. Understanding the available treatment options helps the physician choose the appropriate treatment for each patient. Having a reproducible model for PIH is essential for the development of treatment modalities. The second article in this 2-part continuing medical education series on PIH specifically addresses the evidence that supports medical and procedural treatments of PIH and other forms of acquired hyperpigmentation. It also describes a PIH model and provides an algorithm for clinical practice along with discussion about the prevention of PIH.

Evidence for Anti-Aging South Korean Cosmeceuticals.

As the market for South Korean skin care products grows in the U.S. and worldwide, consumers will increasingly seek advice from dermatologists regarding their efficacy. In this paper, the evidence behind the anti-aging and skin whitening activity of ingredients in the most popular South Korean skin care products was reviewed and critically evaluated. Industry profit data from Euromonitor was obtained to identify the top cosmeceutical brands by retail value in South Korea. The top selling products and their ingredients were then identified from individual brand websites. A comprehensive literature search was conducted using Pubmed to identify and grade the anti-aging and whitening efficacy for nine popular ingredients: licorice, niacinamide, beta-glucan, snail mucus, ginkgo biloba, ginseng, green tea, pomegranate, and soy. Of the various ingredients reviewed, niacinamide, green tea, licorice, and soy have the most published data for anti-aging and whitening activity. Although the literature shows modest results, small sample sizes limit interpretation. High-level evidence to support the use of South Korean skin care products in anti-aging and skin whitening is lacking.

J Drugs Dermatol. 2017;16(4):358-364.

A Prospective Trial Comparing Q-Switched Ruby Laser and a Triple Combination Skin-Lightening Cream in the Treatment of Solar Lentigines.

BACKGROUND: Quality-switched (QS) laser therapy is a safe and well-established treatment option for removing solar lentigines. Triple combination therapy (TCT) with the active pharmaceutical ingredients hydroquinone 5%, tretinoin 0.03%, and dexamethasone 0.03% is often used for skin-lightening. OBJECTIVE: This prospective, open-label trial compares the efficacy and safety of a QS Ruby laser (QSRL) and a TCT in the treatment of solar lentigines. METHODS: In total, 15 patients with symmetrically distributed solar lentigines on the back of both hands were included. The lesions on the back of the right hand were treated in one or 2 sessions with a QSRL, the ones on the back of the left hand with a TCT for 7 weeks accompanied by UV protection. Clinical results were evaluated 4 weeks, 8 weeks, and 20 weeks after baseline. RESULTS: Treatment with QSRL provided significant lightening (p = .01) compared with TCT. Both procedures were generally well-tolerated. Comparing the side effects, the laser produced significantly more crusting and hyperpigmentation than the TCT. CONCLUSION: Both QSRL and TCT were capable in reducing solar lentigines in Fitzpatrick skin Type I to IV with an acceptable side effect profile. The QSRL provides faster, superior, and long lasting lightening compared with TCT.

A split-face evaluation of a novel pigment-lightening agent compared with no treatment and hydroquinone.

BACKGROUND: Lignin peroxidase is a cosmetic skin-lightening alternative that breaks down plant cell walls and melanin. OBJECTIVE: This research examined the topical efficacy of lignin peroxidase in pigment lightening. METHODS: Sixty women aged 18 to 65 years with mild to moderate facial dyspigmentation were enrolled for 12 weeks in 2 cohorts. Cohort 1 applied lignin peroxidase to 1 randomized side of the face and nothing to the opposite side. Cohort 2 applied lignin peroxidase to 1 facial side and generic hydroquinone to the other. Investigator, subject, and dermospectrophotometer measurements were obtained. RESULTS: In cohort 1, improved skin texture (P < .001), roughness (P < .001), and overall appearance (P = .002) was noted at week 2 with lignin peroxidase versus no treatment. By week 12, there was a decrease in spot size with lignin peroxidase versus no treatment (P = .014). This was confirmed by a statistically significant reduction in melanin scores with the dermospectrophotometer on lignin peroxidase-treated side at weeks 4, 8, and 12 (P = .003) and a similar reduction in Melasma Area Severity Index score. Cohort 2 demonstrated parity between lignin peroxidase and hydroquinone, but lignin peroxidase was statistically superior in skin texture and roughness. LIMITATIONS: The sample size was limited. CONCLUSIONS: Lignin peroxidase might be an over-the-counter skin-lightening preparation with efficacy parity to hydroquinone.

Clinical and instrumental evaluation of the efficacy of a new depigmenting agent containing a combination of a retinoid, a phenolic agent and an antioxidant for the treatment of solar lentigines.

BACKGROUND: Solar lentigines are common benign macular hyperpigmented lesions localized on sun-exposed areas. OBJECTIVE: To evaluate the efficacy and safety of a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (δ-tocopheryl-ß-D-glucopyranoside) in the topical treatment of solar lentigines. PATIENTS AND METHODS: Twenty patients with solar lentigines of the face and hands applied the depigmenting agent on each lentigo once daily for 12 weeks. The outcome was evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared to baseline (T0) by means of clinical evaluation, Mexameter® and Visioface devices for digital and ultraviolet computerized image analysis of skin color as well as in vivo reflectance confocal microscopy. RESULTS: Image analysis and confocal laser reflectance microscopy showed that hyperpigmentation was significantly reduced at T2 compared to baseline and to controls. CONCLUSION: The study treatment was well tolerated and showed significant improvement in the depigmentation of solar lentigines.