BACKGROUND:To meet the unique needs of aging skin of the neck, a new neck cream that enhances nitric oxide availability has been developed to visibly improve signs of aging and overall quality of skin.METHODS:The primary objective of this dual center, open label clinical trial was to assess the efficacy and tolerability of the new neck cream applied twice daily over 12 weeks in aging women with mild-to-moderate lines and wrinkles of the neck (Group 1, N=26). A second group with mild-to-moderate lines and wrinkles and photodamage of the neck and décolleté (Group 2, N=10) applied the neck cream (AM/PM) in combination with a double-conjugated retinoid/alpha hydroxy acid (AHA-Ret; PM) to both the neck and décolleté over 12 weeks.RESULTS:Group 1 demonstrated significant improvements from baseline in the neck of 21% (P=.007) for wrinkles and lines, 27% (P=.004) for skin texture, and 26% (P=.003) for skin tone at 12 weeks. Significant improvements were also observed at 4 and 8 weeks. In Group 2, significant improvements were observed from baseline in the neck and décolleté areas with a 34% (P=.01) improvement in photodamaged skin in the décolleté area. The neck cream was well tolerated with few mild and transient adverse events.CONCLUSION:A new neck cream formulated to enhance nitric oxide availability to the skin when applied alone or in combination with AHA-Ret provided statistically significant improvements from baseline in skin appearance of the neck and décolleté, most notably in lines and wrinkles, skin texture, and skin tone.CITATION:Robinson DM, Kaufman J, Giannini A, et al. Evaluation of a neck cream developed to enhance nitric oxide availability in aging skin. J Drugs Dermatol. 2023;22(9):881-886. doi:10.36849/JDD.7210.

Introduction: The periorbital region is susceptible to premature skin aging and among the first areas to manifest age-related changes. Retinoids are highly effective but can be irritating, limiting use in this vulnerable area. A hydrating formulation comprised of a double-conjugated retinoid/alpha hydroxy acid (lactic acid; AHARet-EM) has been developed to address photoaging of the periorbital area. This study evaluated the efficacy, tolerability, and subject satisfaction of nightly application of AHARet-EM, and a regimen that included application of a peptide-rich eye cream (InF-E; AM) and AHARet-EM (PM). Design: A 12-week, dual-center, open-label study evaluated nightly application of AHARet-EM in subjects 35 to 65 years of age with fine to moderate lines/wrinkles in the periorbital area (3-7 score based on the Fitzpatrick Classification Wrinkle Scale [FCWS1). A subset of subjects applied AHARet-EM (PM) and InF-E (AM). Investigator assessments at baseline and weeks 4, 8, and 12 were based on the 9-point FCWS for lines/wrinkles (1 [Fine Wrinkles] to 9 [Deep Wrinkles]) and a 6-point scale (0 [None] to 5 [Severe]) for texture, erythema, and under-eye darkness, puffiness, and dryness. Subject satisfaction and adverse events (AEs) were captured over 12 weeks. Results: Twenty-six subjects, Fitzpatrick skin type III-VI, completed the study. Subjects applying AHARet-EM (n=16) demonstrated significant improvements from baseline at week 12 in the appearance of lines/wrinkles (33%; P<.0001), texture (37%, P<.0001), erythema (37%, P=.004), under-eye darkness (41%; P<.001), puffiness (55%, P<.0001) and dryness (94%, P<.0001). Significant improvements from baseline were demonstrated in subjects using the AM/PM regimen (n=10) at week 12 in the appearance of texture (33%; P=.002), erythema (68%; P=.001), under-eye darkness (32%; P=.007), puffiness (64%; P=.01) and dryness (90%; P<.0001). No AEs occurred related/possibly related to use of the study products. High levels of subject satisfaction were reported over 12 weeks. Conclusion: Nightly application of a hydrating, double-conjugated retinoid eye cream demonstrated significant improvements in the appearance of lines/wrinkles, under-eye darkness, puffiness, and dryness of the periorbital area at week 12. Morning application of a peptide-rich eye cream afforded additional benefits. The study products were non-irritating, and subjects reported high levels of satisfaction throughout the study.

Background:Topical retinoids influence the rate of cellular turnover and improve skin clarity and photoaged skin. Consequent cutaneous irritation reduces adherence resulting in suboptimal outcomes. A formulation comprised of a double-conjugated molecule containing a retinoid and an alpha hydroxy acid (AHA) has been purposefully developed for individuals with blemish-prone skin. Design and Methods: A 12-week study conducted in subjects with mild/moderate blemish-prone skin evaluated skin clarity utilizing the Investigators Global Assessment Scale (0-Clear to 4-Severe). Changes in the appearance of pores were evaluated using a 6-point scale (0-None to 5-Severe). Adverse Events (AEs) and subject satisfaction were captured. A secondary analysis evaluated visible, quantitative changes in pores. Results: Twenty subjects enrolled; 19 subjects completed the study. Mean percent improvements in appearance from baseline in skin clarity were demonstrated at weeks 4 (43%; P<.0001), 8 (48%; P<.0001) and 12 (50%; P<.0001). Mean percent visible improvements from baseline in pores were observed at 4, 8, and 12 weeks (33% IP<.0001]; 21% (P=.04] and 25% fP=.00061, respectively). AEs were mild and transient. By 8 weeks, all subjects reported improvement in overall appearance and that their skin was healthier looking. Secondary quantitative analysis (n=6) demonstrated an 18% mean improvement in the appearance of pores from baseline at week 12. Conclusions: A double-conjugated retinoid/AHA cream specifically developed for individuals with blemish-prone skin demonstrated early improvements in the appearance of skin clarity and pores over 12 weeks. AEs were mild and transient. Subjects reported high levels of satisfaction in the overall appearance and quality of skin.

Introduction: There is growing interest in skincare products designed to address the unique characteristics of male skin. This study evaluated the efficacy and tolerability of a comprehensive antioxidant product (SHD-M) developed for men.

OBJECTIVE:Skin damage from visible light predominantly results from exposure to the blue light spectrum (400-500 nm) which generates Reactive Oxygen Species (ROS) causing a cascade of harmful effects to skin. Topical antioxidants reduce the effects of free radical damage caused by environmental exposures. This study evaluated a comprehensive topical antioxidant's ability to inhibit ROS production induced by blue light and cigarette smoke (CS) in human skin. METHODS:Two experiments were conducted utilizing human skin (Fitzpatrick Skin Types III and V; N = 3, each). After confirmed reactivity of untreated tissues at 412 nm, 20J/cm2 , untreated and pretreated (WEL-DS, 2 mg/cm2 ) skin tissue was exposed to blue light and blue light plus CS and left overnight. A nonfluorescent probe (DCFH-DA) was added to skin and exposed to blue light (412 nm, 20J/cm2 ) and blue light plus CS. Fluorescent 2',7'-DCF was generated upon enzymatic reduction and subsequent oxidation by ROS. RESULTS:ROS increased at least tenfold following initial exposure to blue light and blue light plus CS in untreated skin. Pretreatment with WEL-DS decreased ROS in FST III exposed to blue light by 51% and 46% in skin exposed to blue light plus CS vs. untreated skin (both, P < .001). In FST V, pretreatment with WEL-DS decreased ROS exposed to blue light by 54% (P < .001) and 50% in skin exposed to blue light plus CS vs. untreated skin (P < .0001). CONCLUSION:WEL-DS demonstrated significant reduction in ROS induced by blue light and blue light in combination with CS compared with untreated, exposed skin.

Introduction There is growing interest in skincare products designed for men. This pilot study evaluated the efficacy and tolerability of a comprehensive antioxidant product in men. Methods This 12-week study evaluated improvements from baseline in erythema, lines/wrinkles, skin tone, texture, brightness, dryness/flaking and pores (6-point scale), global improvements (5-point scale), and sebum levels following daily application in males with mild to moderate photodamaged skin. Subject self-assessments and adverse events (AEs) were captured. Results Twenty-two subjects completed the study. Early mean percent improvements from baseline were demonstrated in all categories at week 4 with visible improvements in skin tone (29%; p = .0001) and pores (28%; p < .0001). Reductions in skin surface sebum levels (forehead region) from baseline were demonstrated at 8 (p < .0001) and 12 (p < .0003) weeks. Ninety-six percent of subjects reported overall visible improvement of their skin and that the study product calmed/soothed skin, reducing redness and irritation after shaving. One subject reported mild dryness. Conclusion Once daily application of a comprehensive topical antioxidant designed for men led to significant improvements in skin appearance, substantial reductions in skin surface sebum levels, and was well tolerated with a high level of subject satisfaction over 12 weeks.

Background: Skin damage from visible light predominantly results from exposure to the blue light spectrum (400-500 nm) which generates reactive oxygen species (ROS) causing a cascade of harmful effects to skin. Topical antioxidants reduce the effects of free radical damage caused by environmental exposures. This study evaluated the ability of WEL-DS, a comprehensive topical antioxidant, to inhibit ROS production induced by blue light and pollution in human skin.

Background and Objective: Three critical elements of skin moisturization and optimal skin barrier health include enhancing skin’s natural lipid bilayer, natural moisturizing factors (NMF) and hyaluronic acid (HA). Herein we evaluated the skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT).

Tropospheric ozone (O3) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O3-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O3 (0.4 ppm, 4 h); Group 3 were pretreated with WEL-DS and unexposed; Group 4 were pretreated with WEL-DS and exposed to O3 (0.4 ppm, 4 h). Pretreated tissues were topically treated with 20 uL of WEL-DS and incubated for up to 20 h at 37 °C [humidified, 5% carbon dioxide (CO2)]. After 24 h, tissues were re-treated with WEL-DS and exposed to O3. Tissues were evaluated for Reactive Oxygen Species (ROS), hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE) protein adducts, NF-κB p65 response and histology. In O3-exposed groups, WEL-DS significantly inhibited ROS formation vs. untreated tissues (p < 0.05). Pretreatment with WEL-DS inhibited H2O2 production vs. untreated tissues (p < 0.05), and decreased NF-κB p65 transcription factor signal. Oxidative stress induction in O3-exposed tissues was confirmed by increased levels of 4-HNE protein adducts (marker of lipid peroxidation); WEL-DS application reduced this effect. WEL-DS inhibited damage in tissues exposed to O3 with no significant changes in epidermal structure. A comprehensive topical antioxidant significantly diminished O3-induced oxidative damage in a human epidermal skin model.

Objective: This study evaluated the effects of twice-daily application of a new rebalancing moisture treatment (TRMT) cream that aims to optimize skin moisturization and enhance skin barrier by supporting skin’s natural lipid bilayer and enhancing NMFs and HA in subjects with moderate to severe photodamaged skin.

Objectives To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin. Methods In an epidermal skin model, tissues (n = 5/group) were topically treated with 25 mu L of TRMT, 25 mu L of a market-leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice-daily application of TRMT, assessing changes in fine lines/wrinkles, brightness, texture, erythema, and tolerability from baseline through week 8. Hydration was measured using electrical impedance. Results TRMT and MLM demonstrated significant increases in hydration vs untreated tissue at each timepoint (P < .005), with greater hydration effects observed for TRMT vs MLM. TRMT-treated tissues demonstrated greater expression of CLD, AQP, and HA, and reduced expression of HYAL vs untreated and MLM-treated tissues. Twice-daily application of TRMT demonstrated significant improvements at 2 weeks in fine lines/wrinkles (P < .001), brightness (P < .0001), texture (P < .0004), and hydration (P < .004). At 8 weeks, statistically significant improvements were achieved in all categories. Conclusion In an epidermal skin model, TRMT demonstrated significant increases in hydration, greater hydration effects, and expression of key markers associated with skin barrier and hydration vs a MLM. Twice-daily application of TRMT was well tolerated and resulted in early, significant improvements in hydration and visible improvements in skin brightness, texture, fine lines/wrinkles, and erythema at 8 weeks.

Objectives: Investigators sought to evaluate the antioxidant capacity of a comprehensive topical antioxidant (WEL-DS), its ability to protect skin against the oxidizing effects of UVA/UVB radiation, and to assess the effectiveness and tolerability of WEL-DS for visible improvements in facial photodamage. Study Designs:In-vitro testing utilized a hydrogen peroxide assay to detect activity in human skin explants following application with WEL-DS, a leading antioxidant serum (L-AOX), and a saline control. Clinical studies included a minimal erythema dose (MED) trial in female subjects, aged 35 to 60 years. Skin was initially irradiated to determine each subject's MED. WEL-DS was applied for four days to one site on the lower back of subjects; the other site remained untreated. Both sites were irradiated with 1X, 2X and 3X each subject's MED, digital images were obtained, and punch biopsies were collected from the 3X MED irradiated areas for histological analysis. A second clinical study evaluated efficacy and tolerability of twice daily application of WEL-DS in female subjects, aged 25 to 65 years with mild-to-moderate photodamage. Changes in fine lines/ wrinkles, dyschromia, erythema, skin tone, pores, and tolerability were assessed at baseline and Weeks 4, 8, and 12. A subset of subjects were evaluated through Week 16. Results: Skin treated with WEL-DS neutralized up to 53 percent more oxidative stress relative to L-AOX. WEL-DS-treated skin demonstrated significantly less UV-induced erythema at 1X, 2X, and 3X MED and demonstrated cellular protective effects versus untreated irradiated skin (N=5). WEL-DS demonstrated average improvements from baseline of 37 percent, fine lines/ wrinkles; 17 percent, skin tone; 13 percent, dyschromia; 18 percent, erythema; and four percent, pores (N=21; Week 12). Continued improvements were demonstrated in all parameters in an extension study (n=14; week 16). WEL-DS was well-tolerated. Conclusion: These studies demonstrate WEL-DS's innate ability to quench free radicals, protect skin from the oxidizing effects of UV radiation, and reduce the visible effects of facial photodamage.

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.

Summary Background Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating. Objective Evaluate the effectiveness and tolerability of a double‐conjugate retinoid cream (AlphaRet Overnight Cream; AHA ‐Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin. Methods A 12‐week, split‐face, randomized trial was conducted in 48 female subjects, aged 30‐65 years with mild to severe photodamage. AHA ‐Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side ( PM ). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study. Results Forty‐seven subjects completed the study. AHA ‐Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles ( P <.001; all time points); Erythema ( P =.004, P <.0001; 8 and 12 weeks, respectively); Dyschromia ( P <.0001; all time points); Skin Tone ( P <.0001; all time points), and Pore Size ( P =.035, P <.0001; 8 and 12 weeks, respectively). AHA ‐Ret induced less Erythema vs retinol at 8 ( P =.008) and 12 ( P <.02) weeks. AHA ‐Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA ‐Ret only ( P <.04, P <.03, P <.01). Less irritation was reported with AHA ‐Ret vs retinol or tretinoin. Conclusions Treatment with a double‐conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA ‐Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.