Article

Clinical Efficacy of 25% L-Ascorbic Acid (C'ensil) in the Treatment of Melasma

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Abstract

L-Ascorbic acid is used to treat melasma; however, it is quickly oxidized in aqueous solutions. Thus, C'ensil, a formulation containing 25% l-ascorbic acid and a chemical penetration enhancer, was created to promote the penetration of l-ascorbic acid into the skin. To evaluate the efficacy of C'ensil in patients with melasma. Forty subjects with melasma were treated with C'ensil during an open-label trial over a period of 16 weeks. Each subject's skin pigmentation was assessed every 4 weeks using the Melasma Area and Severity Index (MASI) and mexameter score. In addition, transepidermal water loss, skin dryness and irritation, and quality of life (Melasma Quality of Life Scale [MelasQoL]) were evaluated. After 16 weeks, a significant decrease was noted in the degree of pigmentation based on the patients' MASI and mexameter scores. MelasQoL scores also decreased, indicating an increase in the subjects' quality of life. Our data indicate that C'ensil is an effective treatment modality for melasma.

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... The analyses showed a reduction in discoloration and in vascular lesions after 28 days of testing for the formulation containing Vit C in comparison with the control formulation (Figure 7). A similar study of the effect of a topical formulation with 25% ascorbic acid and a chemical penetration enhancer showed a significant decrease in pigmentation caused by melasma after 16 weeks of use [62]. The present ex vivo study was conducted for 4 weeks, which may be too short a period of time for the effects of the therapy to be become more visible, in comparison with the study by Hwang et al. ...
... The present ex vivo study was conducted for 4 weeks, which may be too short a period of time for the effects of the therapy to be become more visible, in comparison with the study by Hwang et al. Moreover, in [62] there is no information on the condition of the skin after 28 days of using the preparation. Vit C enhances the endothelial synthesis and deposition of collagen type IV in the formation of the basement membranes of blood vessels [63], reduces their vascular fragility [64] and seals them [65]. ...
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The developing field of bio-nanotechnology aims to advance colloidal research via the introduction of multifunctional nanoparticles to augment the dermal effectiveness of active substances. Self-emulsifying drug delivery systems (SEDDS)—isotropic mixtures of oils, surfactants, solvents and co-solvents or surfactants—are attracting interest in the cosmeceutical field. As part of this study, SEDDS systems containing vitamin C or vitamin E and curcumin were developed, whereby the bioavailability of the active compounds increased by enhancing their permeability to deeper layers of the skin. A composition consisting of 50% surfactin from Bacillus subtilis, 30% Transcutol and 20% oil phase was designed to encapsulate the active substances, i.e., vitamin C or vitamin E and curcumin, contained in the oil phase. The developed carriers were characterized by average particle sizes of 69–183 nm. The formulations with the vitamins were found to be physically and chemically stable for 6 months. Transdermal tests were carried out, showing that the carriers enable the transport of active substances deep into the skin, stopping at the dermis border. The formulations with vitamin C and vitamin E reduced the discoloration, the vascular lesions, and the depth of the wrinkles on the tested skin, which can be useful in cosmetics in the treatment of problem skin, including capillary and sensitive skin.
... Takenouchi K, Aso K (1964) 23 Animal study Yussif NM, Koranayb NS, Abbass MMS (2017) 24 Animal study Matsuda S, Shibayama H, Hisama M, Ohtsuki M, Iwaki M (2008) 25 In-vitro study Panich U, Tangsupaanan V, Onkoksoong T, Kongtaphan K, Kasetsinsombat K, Akarasereenont P et al (2011) 11 In-vitro study Lee SA, Son YO, Kook SH, Choi KC, Lee JC. (2011) 26 In-vitro study Taira N, Katsuyama Y, Yoshioka M, Okano Y, Masaki H (2017) 27 In-vitro study Katsuyama Y, Taira N, Yoshioka M, Okano Y, Masaki H (2018) 28 In-vitro study Taira N, Katsuyama Y, Yoshioka M, Okano Y, Morikawa T (2018) 29 In-vitro study Yim S, Lee J, Jo H, Scholten J, Willingham R, Nicoll J, Baswan SM (2019) 30 In-vitro study Miao F, Su MY, Jiang S, Luo LF, Shi Y, Lei TC (2019) 31 In-vitro study Lee (2008) 32 Case report Sheel V, Purwar P, Dixit J. and Rai P (2015) 33 Case report Postaire E, Jungmann H, Bejot M, Heinrich U, Tronnier H. (1997) 34 Used along with other agents Broekmans WM, Vink AA, Boelsma E, Klöpping-Ketelaars WA, Tijburg LB, van't Veer P, van Poppel G, Kardinaal AF. (2003) 35 Used along with other agents Hwang SW, Oh DJ, Lee D, Kim JW, Park SW (2009) 36 Used along with other agent Dormael RD, Bastien P, Sextius P, Gueniche A, Ye D, Tran C, et al (2019) 37 Used along with other agent Ishikawa Y, Niwano T, Hirano S, Numano K, Takasima K, Imokawa G (2019) 38 Used along with other agents Kim J, Kim J, Lee YI, Almurayshid A, Jung JY, Lee JH. (2020) 39 Used along with other agents Rattanawiwatpong P, Wanitphakdeedecha R, Bumrungpert A, Maiprasert M (2020) 40 Used along with other agents Huh CH, Seo KI, Park JY, Lim JG, Eun HC, Park KC (2003) 41 Used in conjunction with Iontophoresis Shaikh I, Mashood AA (2014) 42 Used in conjunction with fluorescent pulsed light (FLP) Yun IS, Yoo HS, Kim YO, Rah DK (2013) 43 Used for scar reduction Amirlak B, Mahedia M, Shah N (2016) 44 Used for scar reduction melanosomes of melanocytes (MCs), followed by the progressive transfer of this melanin to keratinocytes. ...
... Takenouchi K, Aso K (1964) 23 Animal study Yussif NM, Koranayb NS, Abbass MMS (2017) 24 Animal study Matsuda S, Shibayama H, Hisama M, Ohtsuki M, Iwaki M (2008) 25 In-vitro study Panich U, Tangsupaanan V, Onkoksoong T, Kongtaphan K, Kasetsinsombat K, Akarasereenont P et al (2011) 11 In-vitro study Lee SA, Son YO, Kook SH, Choi KC, Lee JC. (2011) 26 In-vitro study Taira N, Katsuyama Y, Yoshioka M, Okano Y, Masaki H (2017) 27 In-vitro study Katsuyama Y, Taira N, Yoshioka M, Okano Y, Masaki H (2018) 28 In-vitro study Taira N, Katsuyama Y, Yoshioka M, Okano Y, Morikawa T (2018) 29 In-vitro study Yim S, Lee J, Jo H, Scholten J, Willingham R, Nicoll J, Baswan SM (2019) 30 In-vitro study Miao F, Su MY, Jiang S, Luo LF, Shi Y, Lei TC (2019) 31 In-vitro study Lee (2008) 32 Case report Sheel V, Purwar P, Dixit J. and Rai P (2015) 33 Case report Postaire E, Jungmann H, Bejot M, Heinrich U, Tronnier H. (1997) 34 Used along with other agents Broekmans WM, Vink AA, Boelsma E, Klöpping-Ketelaars WA, Tijburg LB, van't Veer P, van Poppel G, Kardinaal AF. (2003) 35 Used along with other agents Hwang SW, Oh DJ, Lee D, Kim JW, Park SW (2009) 36 Used along with other agent Dormael RD, Bastien P, Sextius P, Gueniche A, Ye D, Tran C, et al (2019) 37 Used along with other agent Ishikawa Y, Niwano T, Hirano S, Numano K, Takasima K, Imokawa G (2019) 38 Used along with other agents Kim J, Kim J, Lee YI, Almurayshid A, Jung JY, Lee JH. (2020) 39 Used along with other agents Rattanawiwatpong P, Wanitphakdeedecha R, Bumrungpert A, Maiprasert M (2020) 40 Used along with other agents Huh CH, Seo KI, Park JY, Lim JG, Eun HC, Park KC (2003) 41 Used in conjunction with Iontophoresis Shaikh I, Mashood AA (2014) 42 Used in conjunction with fluorescent pulsed light (FLP) Yun IS, Yoo HS, Kim YO, Rah DK (2013) 43 Used for scar reduction Amirlak B, Mahedia M, Shah N (2016) 44 Used for scar reduction melanosomes of melanocytes (MCs), followed by the progressive transfer of this melanin to keratinocytes. ...
Article
Full-text available
Vitamin C, also known as ascorbic acid, is used as a treatment modality in depigmentation of hyperpigmented spots on the skin and gingiva. This systematic review discusses the studies conducted to assess the effect of Vitamin C on melanin pigmentation. The primary objective was to evaluate the effect of Vitamin C on melanin pigmentation. The secondary objective was to analyze the effect of Vitamin C administration on melanin pigmentation. An electronic database search was conducted from the following databases: PubMed, EBSCOhost, ScienceOpen, EMBASE and Google Scholar. Randomized controlled trials, experimental studies, case-control studies and cohort studies published in peer-reviewed journals in English language were included. Case reports, case series, animal model studies, in vitro studies, studies where Vitamin C was used along with other agents and unpublished research were excluded. Out of 22,580 studies, only 7 studies satisfied the selection criteria. Data extraction sheet was prepared, and the studies were analyzed. Out of the 7 studies analyzed, 1 was a randomized controlled trial and 6 were experimental studies. Vitamin C has been used widely as a depigmenting agent in dermatology. However, there are limited studies conducted on the use of Vitamin C for gingival depigmentation.
... A split-face randomized controlled trial compared ascorbic acid 5% and hydroquinone 4% used on either side of the face for 16 weeks by sixteen patients with melasma. 136 The study found about 62% and 93% improvement with ascorbic acid and hydroquinone, respectively. ...
... It has been demonstrated experimentally that ascorbic acid 25% formulated with a penetration enhancer significantly improves melasma. 136 Topical α-tocopherol 5% or less is mostly used in cosmeceuticals in combination with vitamin C for lightening effect. A significant improvement in melasma and pigmented contact dermatitis lesions was observed with topical vitamins E and C in a double-blind study and results were better with combination compared with either vitamin used alone. ...
Article
Full-text available
Melasma is a common malady affecting all races with a higher incidence in Hispanics, Middle Eastern, Asians and African origin females (Fitzpatrick skin phototypes III‐V). Women are affected much more often than men. Melasma remains a significant cause of cosmetic morbidity and psychosocial embarrassment affecting quality of life necessitating effective and reliable treatment. Unfortunately, treatment remains unsatisfactory due to limited efficacy, adverse effects and relapses after stopping treatment. Although chemical peels, laser and light therapies and dermabrasion may have utility, the evidence available for their efficacy is limited and they often cause post inflammatory hyperpigmentation particularly in individuals with darker skin types. Medical therapies remain mainstay in the management of melasma. The triple combination, hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01% (Triluma, Galderma, Ft. Worth Texas, often modified incorporating different corticosteroids) remains the only US FDA approved treatment for melasma and is the gold standard due its demonstrated efficacy across ethnicities. Oral tranexamic acid alone or in combination with other modalities has also shown significant efficacy. Several cosmeceuticals and botanical extracts used as skin lightening agents have been demonstrated to be useful. Physical sunscreens containing zinc oxide, iron oxide, titanium dioxide, and silicones provide photoprotective and camouflage effect. We propose that a multimodality approach to the treatment of melasma is the most effective treatment approach. This review is focused on the medical therapies for melasma.
... M = ± 0.0038, p < 0.0001) between the gestation course and childbirth and abortion history. According to our research, in cases of pregnancy ending by birth of surveyed child, every second mother (53.8%) had various complications of pregnancy and childbirth, including cases of (100 women surveyed): -pregnancy toxicosis (39); -threat of preterm birth (31); -Weakness of birth activity and application of forceps (25); -Improper placenta previa (19), -operations during delivery (10) -anemia (73); -presence of extra genital pathology (9). ...
... Significant differences from control are identified and the frequency of digestive diseases (87.5 ± 3.7%, n = 70 vs. 45.0 ± ± 11.1%, n = 9), nervous system (73.8 ± 4.9%, n = 59 vs. 25.0 ± ± 9.7%, n = 5), diseases of the endocrine system (51.3 ± 5.6%, n = 41 vs. 25.0 ± 9.7%, n = 5) allergic diseases (40.0 ± 5.5%, n = 32 vs. 5.0 ± 4.8%, n = 5), blood diseases and blood-forming organs (75.0 ± 4.8%, n = 60 vs. 5.0 ± 4.8%, n = 5). ...
... Melasma Quality of Life Scale (MelasQol) scores indicated improved quality of life. 45 Tolerability and side e ects. In the two studies mentioned before, di erent concentrations were used, demonstrating that higher concentrations result in more side e ects. ...
... These were mild and disappeared within two weeks. 45 Ascorbic acid was shown to be well-tolerated and signi cantly less irritating than HQ 4%. 44 Azelaic acid (AZA). ...
Article
Objective: We conducted a review of topical agents currently used in melasma, discussing their mechanism of action, efficacy, safety, and tolerability, with an update on newer treatments. Methods: A systematic review from PubMed database was performed, using PRISMA guidelines. The search was limited to English and Spanish studies that were double or single blinded, prospective, controlled or randomized clinical trials, reviews of literature, and meta-analysis studies. Results: 348 studies were analyzed; 80 papers met inclusion criteria. Triple combination (TC) therapy and hydroquinone (HQ) are still the most well-studied agents with strong evidence-based recommendation. TC therapy remains the gold standard of care based on efficacy and patient tolerability. Evidence has shown ascorbic acid, azelaic acid, glycolic acid, kojic acid, salicylic acid, and niacinamide to be effective as adjuvant therapies with minimal side effects. Tranexamic acid (TA) and cysteamine have become recent agents of interest due to their good tolerability, however more trials and studies are warranted. Less evidence exists for other topical agents, such as linoleic acid, mulberry extract oil, rucinol, 2% undecylenoyl phenylalanine, and epidermal growth factors agents. Limitations: Some studies discussed represented a low sample size, and there is an overall lack of recent studies with larger populations and long-term follow up. Conclusions: TC therapy continues to be the gold standard of care. Topical cysteamine and TA are newer options that can be incorporated as adjuvant and maintenance treatments into a patient's regimen. Cysteamine and topical TA have no known severe adverse effects. Evidence comparing other topical adjuvant treatments to HQ, maintains HQ as the gold standard of care.
... 12 C'ensil (Sage Pharmeceuticals Inc., Shreveport, LA) containing 25% L-ascorbic acid was developed to promote absorption of L-ascorbic acid into the skin, since it is normally rapidly oxidized into an aqueous solution. 13 Melasma patients treated with C'ensil (n = 40) had a significant decrease in their MASI scores and an increase in their quality of life scores. 13 In a separate study, 5% L-ascorbic acid was compared with 4% hydroquinone cream in 16 women with melasma. ...
... 13 Melasma patients treated with C'ensil (n = 40) had a significant decrease in their MASI scores and an increase in their quality of life scores. 13 In a separate study, 5% L-ascorbic acid was compared with 4% hydroquinone cream in 16 women with melasma. Hydroquinone was superior in subjective measurements than ascorbic acid (93% good and excellent results vs 62.5%, respectively, P < .05). 14 There was no statistical difference in colorimetric measures, but side-effects were much greater in the hydroquinone group (68.5% vs 6.2%, respectively). ...
Article
Full-text available
Disorders of facial hyperpigmentation including melasma, postinflammatory hyperpigmentation and solar lentigines are common cutaneous conditions which can have a huge impact on patients' quality of life and often prove difficult to treat. The nascent market of cosmeceutical options provides a potentially safer and efficacious alternative for treating these challenging conditions. These can be used alone or in combination with other established treatments. Many cosmeceutical products are thought to work through inhibition of tyrosinase, a key enzyme of melanogenesis. We discuss the mode of action and provide an up-to-date review of the underlying evidence base for the top 10 cosmeceutical products for hyperpigmentation and melasma. Possible safer and more efficacious cosmeceutical therapies we discuss include thiamidol, kojic acid, vitamin C, arbutin, retinol, nicotinamide, ferulic acid, resorcinol, licorice root extract, and soy.
... Other adverse effects include mottled confetti-like hypopigmentation, irritation and recurrence post-treatment. 23,24 Different modalities have been trialled to treat melasma with variable and limited evidence. These include intense pulsed light (IPL) (560 nm), 23 broad band light (BBL), QS ruby laser (694 nm), non-ablative fractional laser (1550 nm), Q-switched neodymium-doped yttrium-aluminium-garnet laser (1064 nm) (QS-Nd:YAG laser or 1064 QNYL), 24 Pulsed-dye Laser (PDL), erbium glass non-ablative fractional laser (1550 nm) and Erbium:YAG ablative laser (2940 nm). ...
... Pulsed-dye lasers operating in the 585-595nm range have been shown to be effective in treating melasma in conjunction with the QSL compared to QSL alone, in patients who clinically demonstrate signs of vascular melasma. 8,23 This ties in with the increasing understanding of the role that VEGF plays in the pathogenesis of melasma as discussed above. ...
Article
Facial pigmentation remains a clinical challenge for all dermatologists due to similar appearance despite myriad of causes. Facial hyperpigmentation in women is often misdiagnosed as melasma resulting in subpar clinical outcomes due to the lack of identification of the correct cause of the pigmentation and appropriately targeted treatment. Most dermatologists will base their diagnosis on a visual examination. The characteristic appearance of melasma means that the diagnosis is usually straightforward and can be made clinically by a dermatologist. However, Wood’s lamp and dermatoscope may aid diagnosis and help determine the level of melanin deposition. More importantly, these diagnostic tools assist in ruling out differential diagnoses and facilitate appropriately targeted treatment. The article outlines the presentations of melasma, helping amalgamate the findings and rule out common differential diagnoses.
... [47] In an open-label trial, 25% L-ascorbic acid formulated with a penetration enhancer, was found to have a signiÞ cant effect in the treatment of melasma. [48] Ascorbic acid, however, is highly unstable in aqueous solution and stable esters like magnesium ascorbyl-2-phosphate (MAP) have been synthesized. MAP has a protective effect against UVB radiation [49] and it inhibits melanogenesis in vitro and in vivo. ...
Article
Full-text available
Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.
... In another study, a 25% L-ascorbic acid formulated with a penetration enhancer was found to improve melasma significantly. 79 Because of its instability in aqueous solution, esters like magnesium ascorbyl-2-phosphate (MAP) with similar properties have been used. 80 MAP was found to reduce pigmentation significantly in 19 of 34 patients with melasma and senile freckles but only in three of 25 patients with normal skin. ...
Article
By midcentury, the U.S.A. will be more ethnically and racially diverse. Skin of colour will soon constitute nearly one-half of the U.S. population, and a full understanding of skin conditions that affect this group is of great importance. Structural and functional differences in the skin, as well as the influence of cultural practices, produce variances in skin disease and presentation based on skin type. In the skin of colour population, dyschromia is a growing concern, and a top chief complaint when patients present to the physician. A thorough understanding of the aetiology and management strategies of facial hyperpigmentation is of importance in caring for those afflicted and also in the development of new therapies.
... Tyrosinase is the main enzyme responsible for converting tyrosine into melanin, thereby decreasing melanin formation [24]. A clinical study examining the effect of a topical formulation containing 25% ascorbic acid and a chemical penetration enhancer reported a significant decrease in pigmentation caused by melasma after 16 weeks [25]. ...
Article
Full-text available
Ascorbic acid (vitamin C) is a water-soluble vitamin and a recognized antioxidant drug that is used topically in dermatology to treat and prevent the changes associated with photoaging, as well as for the treatment of hyperpigmentation. Ascorbic acid has neutralizing properties of free radicals, being able to interact with superoxide, hydroxyl and free oxygen ions, preventing the inflammatory processes, carcinogens, and other processes that accelerate photoaging in the skin. Current research focuses on the search for stable compounds of ascorbic acid and new alternatives for administration in the dermis. Unlike plants and most animals, humans do not have the ability to synthesize our own ascorbic acid due to the deficiency of the enzyme L-gulono-gamma-lactone oxidase, which catalyzes the passage terminal in the ascorbic acid biosynthesis. To deal with this situation, humans obtain this vitamin from the diet and/or vitamin supplements, thus preventing the development of diseases and achieving general well-being. Ascorbic acid is involved in important metabolic functions and is vital for the growth and maintenance of healthy bones, teeth, gums, ligaments, and blood vessels. Ascorbic acid is a very unstable vitamin and is easily oxidized in aqueous solutions and cosmetic formulations. Ascorbic acid is extensively used as an ingredient in anti-aging cosmetic products, as sodium ascorbate or ascorbyl palmitate. This review discusses and describes the potential roles for ascorbic acid in skin health and their clinical applications (antioxidative, photoprotective, anti-aging, and anti-pigmentary effects) of topical ascorbic acid on the skin and main mechanisms of action. Considering the instability and difficulty in administering ascorbic acid, we also discuss the importance of several factors involved in the formulation and stabilization of their topical preparations in this review.
... So, a topical preparation containing vitamin C has been used successfully in the treatment of melisma which showed significant lightening of melasma at the end of 16 weeks. [41] No adverse effect has been reported. ...
... 9 ME-LASQoL has been adapted and validated in different countries and used in various clinical trials. [10][11][12][13][14][15][16][17][18] Criticisms have been raised about the construction process and application of MELASQoL, including: difficulties in the semantic interpretation of items, having been validated only in women, no prior qualitative analysis of perception about the disease, low representation of the dimension of feelings and selfesteem, lack of psychometric studies in relation to scalability, and temporal stability. 19 These arguments indicate a need for developing new tools for evaluating QoL in melasma. ...
Article
Full-text available
Background: Melasma has a major impact on quality of life. MELASQoL is the only validated specific psychometric instrument to evaluate melasma QoL. Objective: To develop and validate a multidimensional questionnaire for evaluating quality of life related to facial melasma. Methods: Cross-sectional study performed in 2 institutions (public and private) from Brazil. Two focus groups were carried out: 5 board-certified dermatologists and 10 melasma patients, indicating the dimensions and significant units of melasma QoL. The preliminary questionnaire with 49 itens was applied to 154 facial melasma patients. Item reduction was performed by Rasch analysis. Parallel evaluations of clinical (MASI), demographic, and QoL aspects (MELASQoL, DLQI) were performed. The dimensional structure was assessed by confirmatory factor analysis. Temporal stability was tested in a subgroup of 42 individuals within 7-14 days. Results: The mean (SD) age of the 154 interviewed subjects was 39±8 years, and 87% were females. The median (p25-p75) DLQI and MELASQoL were: 2 (1-6) and 30 (17-44). HRQ-Melasma consisted of 19 items distributed in 4 dimensions: Physical/Appearance, Social/Professional, Psychological, and Treatment. Cronbach's alpha for HRQ-Melasma was 0.96, and >0.74 for each dimension. There was high correlation between HRQ-Melasma and DLQI and MELASQoL (rho=0.80 and 0.83), but modest with MASI (rho=0.35). Dimensional structure of HRQ-Melasma was stated by confirmatory factor analysis coefficients. Test-retest analysis disclosed an intraclass correlation coefficient of 0.91 (p<0.01). Study limitations: Single-center study. Conclusions: A specific instrument to evaluate QoL in melasma with multidimensional characteristics was developed and validated, with appropriate psychometric performance.
... There are a lot of treatment alternatives for melasma. Antioxidants, ROS scavengers and inhibitors of ROS production have been used in the treatment of melasma for the prevention of UV-induced melanogenesis 1,[3][4][5][6][7] . However, there has been no study on the antioxidant activity (AOA) of patients with melasma. ...
Article
Full-text available
Background and Design: Melasma is a common, symmetric hypermelanosis characterized by irregular brown to gray-brown macules on the face. It is frequently associated with pregnancy and oral contraceptive consumption. Sunlight and genetic factors play major roles in the pathogenesis of melasma. Human skin exposed to ultraviolet light or environmental oxidizing pollutants become a preferred target of oxidative stress. Topical and oral antioxidants are used to treat melasma. To investigate serum antioxidant capacity in patients with melasma and relationship between antioxidant levels and melasma severity. Materials and Methods: Forty-nine cases of melasma and 35 controls were included in the study. Each patient’s skin pigmentation was assessed using the Melasma Area Severity Index (MASI) and mexameter reading. Serum trolox equivalent antioxidant capacity (TEAC), total antioxidant activity (TAOA), and ferric reducing power (FRAP) were evaluated in patients and controls by spectrophotometric method. Results: TEAC levels were higher in patients than in controls (p
... 26,27 a clinical study examining the effect of a topical formulation containing 25-percent vitamin C and a chemical penetration enhancer reported a significant decrease in pigmentation caused by melasma after 16 weeks. 28 although vitamin C has been shown to suppress melanin production, its clinical effects may not be as effective as other topical products containing hydroquinone. 29 ...
Article
skin, Vitamin C has been shown to protect against photoaging, ultraviolet-induced immunosuppression, and photocarcinogenesis. it also has an antiaging eCect by increasing collagen synthesis, stabilizing collagen fibers, and decreasing collagen degradation. it decreases melanin formation, thereby reducing pigmentation. Vitamin C is the primary replenisher of vitamin e and works synergistically with vitamin e in the protection against oxidative damage. CONCLUSION: Topical Vitamin C has a wide range of clinical applications, from antiaging and antipigmentary to photoprotective. Currently, clinical studies on the efficacy of topical formulations of Vitamin C remain limited, and the challenge lies in ending the most stable and permeable formulation in achieving the optimal results.
... Ascorbic acid can protect against UVA-dependent melanogenesis through the improvement of antioxidant defense capacity of melanocytes, and inhibition of NO production through down-regulation of eNOS and iNOS mRNA [48]. Its clinical efficacy in a 25% cream was assessed in melasma, based on the MASI and Mexameter scores [49]. ...
... Because hydrophilic LAA (Log P = À2.05) has limited skin permeability, there has been a great interest on enhancing its penetration efficiency through stratum corneum (SC) barrier; thus, it can function in epidermis and dermis, where photoageing and inflammation mostly occur. Various methods have been applied for this purpose, such as using stable lipophilic esterified derivatives of [2], optimizing topical formulations [3,4], microneedle [5], electroporation [6] and iontophoresis [7]. ...
Article
Objective: Percutaneous absorption of L-ascorbic acid (LAA) is limited due to its high hydrophilicity and low stability. Here, we investigated the effect of post-dosing sonophoresis (329 kHz, 20 mW/cm(2) ) and heat (36°C) on transdermal delivery of LAA. Methods: Ultrasound/heat, heat and control treatments were applied on skin surface for 2 and 5 min after topical application of C14-labeled LAA aqueous solution. After 15 min post-exposure, radioactivity was measured in tape-striped stratum corneum (TS-SC), epidermis, dermis, and receptor fluid. Since Franz diffusion cell model may have different acoustic response than in vivo human tissues, a novel petri dish model was developed and compared with Franz cell model on the effects of ultrasound/heat treatment on the skin permeability. Results: 5 min ultrasound/heat treatment significantly accelerated skin absorption/penetration of LAA; 2 min treatment showed no enhancement effect on Franz diffusion cell model at the end of experiment. The use of petri dish model significantly increased LAA concentrations in epidermis after 5 min ultrasound/heat treatment, compared to the results of Franz cell model. Conclusion: Combination of ultrasound (329 kHz, 20 mW/cm(2) ) and heat (36°C) significantly enhanced LAA transdermal penetration, when the time of treatment was sufficient (5 min). As petri dish model was designed to simulate acoustic respond of dense human tissue to ultrasound, the difference between Franz cell and petri dish models suggests that the enhancement effect of ultrasound/heat on skin penetration in vivo may be greater than that determined on in vitro Franz cell model. This article is protected by copyright. All rights reserved.
... 9 Vitamin C (Ascorbic acid) is an anti-oxidant and 25% L-ascorbic acid is shown to be an effective treatment modality for melasma. 10 Multivitamins have more antimelanogenic effect than vitamin C. [11] LASERs have been popular this past decade and act by selective photothermolysis, for example, QS-Nd:YAG(1064 nm) destroys melanosomes. Combination of ablative and pigment selective LASERs are also used. ...
Article
Full-text available
Melasma is an acquired hypermelanosis of the skin usually affecting the face and other sun-exposed areas. There is no universally effective specific therapy for the disease and patients find it difficult to choose one treatment modality for them. The main objectives of this study was to determine the age of onset of melasma, treatment seeking behaviours and reasons for treating Melasma in the first place and for not complying with the treatment options for Melasma. A cross-sectional survey was conducted via a self-administered anonymous questionnaire on 100 conveniently selected melasma patients visiting Out Patient Department (OPD) of Sir Ganga Raam hospital Lahore. Out of 100 melasma patients; most being females, the average age of onset of Melasma was 26.42±7.664 years. As a treatment trend 14% sought treatment immediately after melasma while 32% sought no medical treatment/consultation. Cosmetic reason; looking good (72%) and social pressure (12%) contributed the most in seeking treatment for melasma. The most frequently used treatment modalities were; Bleaching agents (69%) and fairness creams (56%) while dermatologists ranked third. Patients used many treatments with less than required compliance to any with major reason being expenses (22%) and long duration of treatment (13%). Public awareness should be employed that melasma is a disease which has to be treated by a dermatologist, and not just a skin darkening to be treated by a lightening agent.
... Ascorbic acid can protect against UVA-dependent melanogenesis through the improvement of antioxidant defense capacity of melanocytes, and inhibition of NO production through down-regulation of eNOS and iNOS mRNA [48]. Its clinical efficacy in a 25% cream was assessed in melasma, based on the MASI and Mexameter scores [49]. ...
... However, due to the unstable nature of vitamin C (rapid oxidation in aqueous solutions on topical application), a formulation containing 25% L ascorbic acid and chemical penetration enhancer was evaluated for efficacy and stability in melasma patients. [41] 40 patients were treated in an open, uncontrolled trial with a commercial preparation applied topically for 16 weeks, and patients were assessed every 4 weeks using MASI and mexameter scoring There was significant decrease (P < 0.05) in the degree of pigmentation by both parameters, and also an improved quality of life was noted with decrease in melasQOL scores. ...
Article
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Melasma is one of the most common and distressing pigmentary disorders presenting to dermatology clinics. The precise cause of melasma remains unknown; however, there are many possible contributing factors. It is notably difficult to treat and has a tendency to relapse. The existing and most tried topical therapy is hydroquinone and the triple combination with tretinoin and corticosteroids, which is considered the gold standard for melasma. Besides that, azelaic acid, kojic acid, arbutin, ascorbic acid, glycolic acid and salicylic peels have also been tried with limited success. However, multiple novel topical agents are being investigated for their potential as hypopigmenting agents with unique mode of action. But, further trials are required to study their efficacy and safety before they can be further recommended. The article highlights these newer formulations and also briefly mentions about the newer chemical peels and the much hyped lasers in treating this difficult and frustrating condition.
... In a study, patients who used C'ensil, a serum containing ascorbic acid, experienced a significant decrease in pigmentation and improved quality of life after therapy. 11 Kim et al investigated a chemical peel containing vitamin C and found significant improvement in hyperpigmentation for patients with melasma. 12 Hakozaki et al studied a skin-lightening gel containing ascorbyl glucoside and niacinamide. ...
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Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.
... Vit C is also a skin-whitening ingredient, able to interfere with the tyrosinase active site, a fundamental enzyme in melanin production (Pullar et al., 2017). Laboratory and clinical studies showed the successful application of this molecule in the treatment of melasma and hyperpigmentation (Hwang et al., 2009;Stamford, 2012). ...
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Emulsified systems are widely used for topical delivery with the aim of optimizing cutaneous absorption and offering a pleasant sensory. They also may provide a protection of the active molecule against oxidation and/or degradation. The oil phase of o/w emulsions may consist of liquid crystalline structures, especially lamellar structures which are similar to those found in the stratum corneum lipids. In the present work, o/w emulsions containing liquid crystals of mixed cetyl alcohol and Polysorbate 60 were developed for topical delivery of vitamin C, a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. In addition to the well-documented lipid supplementation of the stratum corneum, the liquid crystal emulsions provide a significant chemical stabilization of vitamin C against its degradation. Emulsions were characterized by X-ray diffraction, polarized optical microscopy, and transmission electron microscopy. The stability of vitamin C in the formulations was evaluated upon storage in different conditions of temperature. The emulsions contain a complex colloidal structure, consisting of lamellar liquid crystalline (Lα) and crystalline lamellar gel (Lβ) phases, that provide a very efficient protection of vitamin C against its degradation.
... Moreover, previous studies demonstrated significant improvement with active treatment greater than the control for fine wrinkles, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features [2]. In a clinical study examining the effect of a topical formulation containing 25% vitamin C and a chemical penetration enhancer, Hwang et al. reported a significant decrease in pigmentation caused by melasma after 16 weeks [33]. Moreover, Traikovich et al., in a 3-month daily regimen of topical AA, noted significant objective and subjective improvement in photodamaged facial skin [2]. ...
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Vitamin C is one of the naturally occurring antioxidants capable of reducing or preventing skin photoaging. Achieving a stable formulation with the optimal dose of ascorbic acid to ensure a biologically significant antioxidant effect is a challenge when developing cosmetic formulations. The objective of this study was to develop a stable formula in a non-aqueous media with 15% pure vitamin C supplemented with ginger and to study its efficacy, skin tolerance, and cosmetic assessment in 33 women. Vitamin C stability over time was determined via a high-performance liquid chromatography (HPLC) technique versus an aqueous option. Reactive oxygen species (ROS) determination was quantified to provide antioxidant effect. A 56-day in vivo study was performed to evaluate skin luminosity and hyperpigmentation reduction. Skin acceptability was verified by a dermatologist. The HPLC studies demonstrated a high stability of the anhydrous formula compared to an aqueous option. The in vitro studies showed a reduction in ROS of 93% (p-value < 0.0001). In vivo, luminosity increased by 17% (p-value < 0.0001) and skin tone became 10% more uniform (p-value < 0.007). Moreover, very good skin tolerance was determined as the dermatologist did not determine any clinical signs, and the subjects did not report any feelings of discomfort. We were able to develop an anhydrous formula of pure vitamin C that combines very good stability, consumer acceptance, and skin tolerance with a high level of efficacy.
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Background Several methods of treatment are available for patients with melasma but none are satisfactory. Ascorbic acid is used for the treatment of various skin problems. However, ascorbic acid has limited stability and permeability, and development of ascorbic acid derivatives with improved properties is needed. Objective The aim of the study was to assess the clinical efficacy and safety of different concentrations of ascorbic acid cream in the treatment of melasma. Patients and methods This study included 40 patients with different clinical varieties of melasma, such as centrofacial and malar. The patients were divided equally into four groups: groups I, II, III, and IV. The first three groups were treated with different concentrations of ascorbic acid cream (5, 10, and 25%), whereas the fourth group were treated with topical placebo and served as the control group. Melasma was evaluated with modified melasma area and severity index and patients were followed up for a period of 6 months. Results Significant improvement in melasma (reduction in modified melasma area and severity index score) was observed with all ascorbic acid preparations in comparison with the control group, which showed no response. Group III treated with 25% ascorbic acid gave the best results, followed by the group treated with 10% ascorbic acid and the group treated with 5% ascorbic acid; however, there were nonstatistically significant differences between the three groups. The patients with epidermal melasma showed better response than those with mixed and dermal types. Conclusion Ascorbic acid topical formulations can effectively treat melasma especially with 10 and 25% concentration with minimum and tolerable adverse effects.
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Complementary and alternative medicine (CAM) is a group of non-traditional medical practices that includes natural products, manipulations, and mind and body medicine. CAM use has grown and become popular among patients. In dermatology, honey, green tea, and vitamin C have been used as topical treatments for a variety of diseases. We performed a systematic review to explore the cutaneous effects of each of these three products. Honey's unique antibacterial, anti-inflammatory, and antioxidant properties were shown to contribute to wound healing, especially in ulcers and burns. Green tea, among many health benefits, demonstrated protection from ultraviolet-induced events, such as photoimmunosuppression and skin cancer growth. Vitamin C, known for its antioxidant properties and key role in collagen production, has been shown to produce positive effects on skin hyperpigmentation and aging. Future large well-designed clinical trials are needed in order to further investigate the potential of these agents as dermatological therapies.
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Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis.
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Ilaria Ghersetich, Andrea Bassi, Silvia Betti, Piero Campolmi, and Torello Lotti review the literature with regard to treatment options for melasma, as well as offering a scientific background to the condition. Introduction: Melasma is a typical hypermelanosis, and quite a common dermatological skin disease, which involves sun exposed areas of the skin and mostly affects women of reproductive age. Hyperpigmentation is the result of an increase in cutaneous melanin deposition. Method: Different treatment options are currently available for melasma. This article aims to review the literature pertaining to these treatment options to inform evidence-based practice. Discussion: In mixed and epidermal melasma, the increasingly popular combination of chemical peels (especially superficial – 30% salicylic acid and 10% tretinoin mask) with pharmacologic treatment (hydroquinone, azelaic acid, kojic acid) is a good treatment option. In dermal melasma, physical treatments can be considered, such as intense pulsed light therapy (even though only temporary and transient results are achieved in the authors’ experience), or with fractional laser skin resurfacing (fractional photothermolysis), a new approach using vascular lasers for skin rejuvenation. Conclusions: Melasma continues to be a challenge with regard to treatment options. All melasma patients should be made aware that ultraviolet exposure is a significant triggering or aggravating factor in the development of melasma. The choice of treatment in the melasma patient should take into account the type of melasma to be treated, the skin complexion of the patient, and possible previous treatments.
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Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment. The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.
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L-ascorbic acid has been widely used to treat photo-aged skin. However, its aqueous formula is prone to oxidation. Therefore, a new formula that contains 23.8% L-ascorbic acid and a chemical penetration enhancer was developed. Observe the efficacy and safety of topical 23.8% L-ascorbic acid serum on photo-aged skin. Twenty Chinese women with photo-aged skin were enrolled in this split-face study. They were treated with topical L-ascorbic acid serum with iontophoresis on one side of the face once a day for 2 weeks; the other side of the face was spared treatment through participants' self-control. Changes in photo-aged skin were evaluated using a global evaluation, an overall self-assessment, a spectrophotometer, the phase-shift rapid in vivo measurement of skin (PRIMOS) 3D, and a corneometer. Sixteen of 20 patients (80%) experienced a score decrease of 2 or 3 grades, according to the dermatologist. Fifteen patients (75%) rated their overall satisfaction as excellent or good. Dyspigmentation, surface roughness, and fine lines on the treated side improved significantly. Topical 23.8% L-ascorbic acid serum is effective for the treatment of photo-aged skin and does not cause any obvious side effects.
Article
Background and Objectives To determine the safety and efficacy of a 50 ns Q switched Nd YAG laser vs. a 5 ns Q switched Nd YAG laser for clearance of melasma. To compare subject satisfaction, efficacy, and comfort level between the two lasers.Study Design/Materials and Methods This is a prospective, randomized split face clinical study. The study was approved by the Scripps IRB. Ten healthy female subjects with moderate to severe melasma were enrolled. Each subject had three laser treatments one month apart. Patients were followed up approximately 1 month, 3 months, and 6 months after the final laser treatment. A treatment session consisted of a microdermabrasion, 1064 nm QS laser, and topicals. Subjects were asked to rate treatment pain based on a numerical scale range 0–10 (0 = no pain and 10 = worst pain). A melasma area and severity index (MASI) grading system was applied. Also, melanin measurements were acquired by a reflectance spectrophotometer. Side effects were documented during the study including post treatment erythema.ResultsEight patients completed the study. Subjects showed improvement on both sides of the face. From baseline to 1 month post the final laser treatment, the average MASI scores showed a 16% reduction for the 50 ns QS 1064 nm laser vs. a 27% reduction for the 5 ns QS 1064 nm laser (both significant versus baseline pigment, P < 0.05). This difference in MASI scores between the two lasers was not statistically significant (P = 0.87930). Laser treatments displayed mild erythema that resolved after one day. The melanin meter measurements showed a reduction in pigment readings on both sides. Three months after the final treatment there was some relapse in the melasma, as the mean pigment reduction fell to 12% for the 50 ns laser and 11% for the 5 ns laser. By 3 months pigment reduction was not statistically significant for either laser, and no significant differences in pigment reduction were noted between the two pulse durations. There was a statistically significant difference (P < 0.05) in pain scores reported by the subjects (scale 0–10), the mean pain score for 50 ns QS 1064 nm laser was 1.2 and for the 5 ns QS 2.9 the score was 2.9.Conclusions In this study, we showed that a combination of microdermabrasion, QS1064 nm laser, and topicals decreased the MASI and meter scores without clinically significant side effects. Moreover, the longer pulsed Q switched 1064 nm laser i.e. (50 ns) was associated with less pain than its shorter pulse width counterpart. Lasers Surg. Med. © 2014 Wiley Periodicals, Inc.
Article
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Melasma, a hypermelanosis of the face, is a common skin problem of middle-aged women of all racial groups, especially with dark complexion. Its precise etio-pathogenesis is evasive, genetic influences, exposure to sunlight, pregnancy, oral contraceptives, estrogen-progesterone therapies, thyroid dysfunction, cosmetics, and drugs have been proposed. Centro-facial, malar, and mandibular are well-recognized. Epidermal pigmentation appears brown/black, while dermal is blue in color, and can be distinguished by Wood's lamp illumination. The difference may be inapparent with mixed type of melasma in skin types V and VI. An increase in melanin in epidermis: basal and suprabasal layers and/or dermis is the prime defect. There is an increased expression of tyrosinase related protein-1 involved in eumelanin synthesis. The use of broad-spectrum sunscreen is important, lightening agents like retinoic acid (tretinoin), azelaic acid, and combination therapies containing hydroquinone, tretinoin, and corticosteroids, have been used in the treatment of melasma, and are thought to have increased efficacy as compared with monotherapy. Quasi-drugs, placental extracts, ellagic acid, chamomilla extract, butylresorcinol, tranexamic acid, methoxy potassium salicylate, adenosine monophosphate disodium salt, dipropyl-biphenyl-2,2'-diol, (4-hydroxyphenyl)-2-butanol, and tranexamic acid cetyl ester hydrochloride, in addition to kojic and ascorbic acid have been used. Chemical peeling is a good adjunct. Laser treatment is worthwhile.
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The cultural practice of skin bleaching is highly prevalent in Africa. Most reported cases of toxic effects of skin-lightening products occur in this region. To describe cases of misuse of over-the-counter (OTC) cosmetic skin-lightening products occurring in Canadian immigrants. Two cases of Canadian immigrants with severe complications from OTC skin-bleaching agents were identified in a community-based dermatology practice in Toronto. The case histories were reviewed and analyzed. A 28-year-old African-Canadian woman developed extensive striae from long-term use of a topical cream containing clobetasol that she had purchased in a Caribbean health food store. A 55-year-old African-Canadian woman developed exogenous ochronosis from the use of a topical bleaching agent she had purchased in Ghana. Cosmetic skin lightening with unregulated topical products occurs in Canada. Dermatologists working in Canada need to be aware of this practice to provide appropriate directive care.
Article
Facial melanoses (FM) are a common presentation in Indian patients, causing cosmetic disfigurement with considerable psychological impact. Some of the well defined causes of FM include melasma, Riehl's melanosis, Lichen planus pigmentosus, erythema dyschromicum perstans (EDP), erythrosis, and poikiloderma of Civatte. But there is considerable overlap in features amongst the clinical entities. Etiology in most of the causes is unknown, but some factors such as UV radiation in melasma, exposure to chemicals in EDP, exposure to allergens in Riehl's melanosis are implicated. Diagnosis is generally based on clinical features. The treatment of FM includes removal of aggravating factors, vigorous photoprotection, and some form of active pigment reduction either with topical agents or physical modes of treatment. Topical agents include hydroquinone (HQ), which is the most commonly used agent, often in combination with retinoic acid, corticosteroids, azelaic acid, kojic acid, and glycolic acid. Chemical peels are important modalities of physical therapy, other forms include lasers and dermabrasion.
Article
The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2).
Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.
Article
Hyperpigmentation disorders of the skin are a group of disorders characterized by abnormally darker skin that results from increased melanin production from normal melanocytes. The most common of these disorders are melasma and postinflammatory hyperpigmentation. Hyperpigmentation disorders of the skin are common and especially melasma and postinflammatory hyperpigmentation on face and neck can be a significant cosmetic problem and psychosocial distress for patients. Treatment of hyperpigmentation disorders can be a long lasting process and is more difficult particularly in dark-skinned individuals. Therapeutic goals for therapy include promoting the degredation of melanosomes and retarding the proliferation of melanocytes. Although, current treatment of hyperpigmentation includes multiple modalities with satisfactory cosmetic results for epidermal disorders for hyperpigmentation, there are potentially significant adverse-effects associated with treatment. Dermal disorders of hyperpigmentation are difficult to treat and have not been successfully treated by using currently available therapies. Recognizing the underlining cause is critical for the treatment of hyperpigmentation in order to choose the best-suited therapy for the patient. Because sun exposure is an important etiologic factor in hyperpigmentation, all patients should use daily, broad-spectrum, high SPF sunscreens and minimize sun exposure. Topical applications including phenols, retinoids, corticosteroids and their combinations are the basic treatment of hyperpigmentation. Also other topical bleaching agents (azaleic acid, tazarotene...etc), chemical peels, laser therapy and sunscreens are used for hyperpigmentation therapy. Updated information on hyperpigmentation therapy is presented in this review.
Chapter
Several depigmenting agents are now available both for topical and systemic use with varying degrees of evidence on their efficacy and safety. These agents act by inhibiting melanogenesis, interrupting melanosome transfer, accelerating epidermal desquamation with melanin turnover, antioxidant effects and by other methods. The topical agents that act mainly by inhibiting melanogenesis through tyrosinase inhibition include hydroquinone and derivatives, arbutin, kojic acid, azelaic acid, methimazole, gentisic acid, flavonoids (aloesin, licorice) and antioxidants (ascorbic acid, alpha tocopherols and grapeseed extracts). Examples of agents that interrupt melanosome transfer are niacinamide, soybeans and lectins. Topical agents that accelerate epidermal desquamation and melanin turnover include retinoids, hydroxy acids, salicylic acids and linoleic acids. Other agents that act by varying mechanisms are tranexamic acid, steroids and other active ingredients found in various plant extracts. Topical therapies in combination are found to be more effective as add-on agents to optimise the effects of the other agents and mitigate the side effects of primary agents. They are often used as first-line therapy. The systemic agents used include tranexamic acid, glutathione, oral vitamin C and vitamin E. Some systemic agents such as glutathione are often misused without adequate evidence of its efficacy and long-term safety.
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To evaluate and compare the effects of subgingival application of ozone gel and chlorhexidine gel in combination with traditional mechanical therapy in patients with plaque induced gingivitis undergoing orthodontic therapy. 20 subjects aged 15-40 were randomized by a simple method of alternatively assigning them to the test and control group in 1:1 ratio. In the control group 10 patients undergoing Orthodontics treatment with inflamed gingiva were selected for scaling and 1 ml of 0.2% Chlorhexidine gel was delivered subgingivally. In the test group10 patients undergoing Orthodontic treatment with inflamed gingiva were selected for scaling and 1 ml of Ozone (70 mcg/ml) gel was delivered subgingivally. Both the therapeutic approach showed significant (p<0.05) reduction in plaque index, gingival index and sulcus bleeding index when compared from baseline to 3 months. Both the therapeutic approaches led to significant reduction in microbiological colony count when compared from baseline to 3 months. On intergroup comparison Ozone Group showed higher reduction in GI, PI, SBI as compared to Chlorhexidine group but the difference was statistically non-significant. ozone gel can be an effective and practical alternative to chlorhexidine gel.
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Vitamin C (L-Ascorbic acid) has many favorable effects on the skin such as antioxidant, anti-aging and whitening effects. Its instability and low permeability limit its pharmaceutical use in cosmetic and dermatological products. Instead, Mg ascorbyl phosphate (MAP), an ascorbic acid derivative, has the same effect with higher stability is being used. In this work, a vesicular system, aspasomes, containing MAP was developed and evaluated. Aspasomes are multilayered vesicles formed by amphiphiles molecules, Ascorbyl palmitate (ASP), in combination with cholesterol and charged lipids for drug encapsulation. Here, we investigated the use of lecithin instead of the charged lipid dicetyl phosphate for aspasomes development. Nine formulations were prepared and evaluated for their entrapment efficiency, particle size, polydispersity index (PDI) and zeta potential. Their entrapment efficiency ranged from 33.00 ± 2.27 to 95.18 ± 1.06 while their particle size was from 373.34 ± 60.85 to 464.37 ± 93.46 nm with acceptable PDI (from 0.212 ± 0.068 to 0.351 ± 0.061) and zeta potential (from -37.52 ± 2.42 to -50.36 ± 1.82). Three formulations were selected and evaluated for their drug release, permeation and retention into skin. One formulation was selected to be formulated as aspasomal topical cream and gel. The aspasomal cream was found to have enhanced drug permeation and skin retention over the aspasomal gel as well as the aspasomes formulation. MAP aspasomal cream was evaluated clinically as an effective treatment for Melasma against 15% Trichloroacetic acid (TCA) and the results recorded that the aspasomal cream showed the greatest degree of improvement regarding the hemi- MASI scores with 35% of patients rating it as excellent treatment. The study showed that MAP aspasomal cream can be considered a novel treatment of melasma which is free of side effects. Its efficacy as a monotherapy is superior to that of chemical peeling using 15% TCA.
Article
Background Sunscreens have long been an indispensable part in treating melasma as ancillary agents. None of previous studies have evaluated the role of sunscreens alone in the improvement of melasma. Aims Our objective was to study the role of broad‐spectrum sunscreen with sun protection factor 19 and PA+++ as the sole agent for improvement of melasma. Methods A total of 100 patients with melasma were included in the study. Following proper method of application of 3 mL sunscreen, thrice daily, Melasma Area Severity Score (MASI) and Hindi language version of the MELASQOL scale (Hi‐MELAQOL) was done at baseline and 12 weeks. Results The mean MASI in the study group at the beginning and at the end of the study was 12.38 ± 14.7 and 9.15 ± 4.7, respectively, whereas the mean value of Hi‐MELASQOL at the beginning and at the end of the study was 47.2 ± 14 and 38.1 ± 14.2, respectively. The differences of both were statistically significant. Spearman's correlation between MASI and Hi‐MELASQOL before and after the study was positive but insignificant. Conclusion There was both an objective and subjective improvement in melasma after 12 weeks of sunscreen use in terms of both MASI, showing an objective improvement of melasma after using sunscreens alone and also in Hi‐MELASQOL showing that use of sunscreens significantly improved quality of life of melasma patients. In our study, we have attempted to re‐instate the importance of sunscreens to patients and dermatologists who are inclining more toward various skin lightening agents for treatment of melasma, which have many side effects.
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Introduction: Melasma is a common pigmentary disorder affecting the face. Although a few risk factors have been identified, the exact pathogenesis remains elusive. Many treatment modalities have been tried, but none have been completely successful. Aim: To compare safety and efficacy of microneedling with Tranexamic acid versus microneedling with Vitamin C in the treatment of melasma. Materials and methods: It was a split face, comparative study conducted on 30 female melasma patients. After obtaining informed consent, microneedling with Tranexamic acid was done on left side and microneedling with Vitamin C was done on right side of face. The improvement was evaluated on the basis of clinical photographs, MASI, Physician Global Assessment (PGA) and Patient Global Assessment (PtGA) at each visit (0, 4 and 8 weeks). Z test was used to test the significant difference in the means of the 2 groups at 4 weeks and at 8 weeks. Results: At the end of 8 weeks, MASI, PGA and PtGA showed improvement with both tranexamic acid and vitamin C. However the improvement was more with tranexamic acid than with vitamin C, although not statistically significant. Conclusion: Both TXA and Vitamin C are effective and safe treatments for melasma. But, TXA was found to be more effective.
Article
Extensive melanin production and accumulation inside the skin may result in a number of disorders, among which is acquired hyperpigmentation, such as melasma. Skin hyperpigmentation is attributed to either the increase in the number of melanocytes or the hyperactivity of melanogenic enzymes. Genetic susceptibility, ultraviolet radiation, hormonal remedies as well as the abnormal release of the α-melanocyte stimulating hormone (α-MSH) represent the provoking factors contributing to such disorder. On the account of their prominent localization in skin-exposed areas, hyperpigmentation may possess cosmetic and psychosocial relevance, and subsequently many efforts have been exerted to help rectify this skin disorder. The current review presents the approaches adopted to treat melasma. It also reviews the active molecules counteracting the melanogenesis process and the diverse nanotechnology-based delivery systems, which showed successful topical delivery of hypopigmenting agents for the treatment of melasma.
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Melasma, a common cause for seeking dermatologic care, is a chronic condition of skin hyperpigmentation. With a poorly understood pathogenesis, and no universal cure, melasma is a challenge for many dermatologists. For decades, there has been investigation into the role of oxidative stress in melasma. In this literature review, we introduce the role of oxidative stress in melasma and discuss the function of various topical and oral antioxidant therapies for patients suffering from melasma. Numerous studies have shown efficacy of various antioxidant therapies for treatment of hyperpigmentation, and in this review, we focus primarily on those with less widespread use. Vitamin E, niacinamide, polypodium leucotomos, pycnogenol, grape seed extract, amino fruit acids, phytic acid, zinc, silymarin, Korean red ginseng powder, plant extracts, and parsley all have well‐demonstrated evidence of antioxidant properties, and these substances have been studied in the context of skin hyperpigmentation. Although there is conflicting evidence of their therapeutic efficacy, the use of these naturally occurring substances is promising for patients and medical providers seeking alternative therapeutic options.
Article
Background Hyperpigmentation disorders are commonly encountered in dermatology clinics. The use of prescription-grade and over-the-counter topical lightening agents have increased in popularity, leading to a substantial growth of research over the past decade. Objective We seek to review clinical studies evaluating the use of different Rx-grade and OTC ingredients in treating hyperpigmentation. Methods & Materials: A comprehensive search on PubMed was conducted to identify patient-based evidence on the most common ingredients used as topical lightening agents: arbutin, ascorbic acid, cysteamine, hydroquinone, kojic acid, niacinamide, retinoids, triple-combination therapy. The topicals were classified as either prescription-grade or over-the-counter. Results Varying levels of evidence support the use of topicals in treating hyperpigmentation. There were more clinical trials examining Rx-grade products than OTC products. Mild but tolerated side effects are noted in many of these agents. Conclusion Careful monitoring and adjustment of doses will be needed to maximize skin lightening benefits and minimize side effects.
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Standing amidst the COVID-19 pandemic, we have faced major medical and economic crisis in recent times which remains to be an unresolved issue till date. Although the scientific community has made significant progress towards diagnosis and understanding the disease; however, effective therapeutics are still lacking. Several omics-based studies, especially proteomics and interactomics, have contributed significantly in terms of identifying biomarker panels that can potentially be used for the disease prognosis. This has also paved the way to identify the targets for drug repurposing as a therapeutic alternative. US Food and Drug Administration (FDA) has set in motion more than 500 drug development programs on an emergency basis, most of them are focusing on repurposed drugs. Remdesivir is one such success of a robust and quick drug repurposing approach. The advancements in omics-based technologies has allowed to explore altered host proteins, which were earlier restricted to only SARS-CoV-2 protein signatures. In this article, we have reviewed major contributions of proteomics and interactomics techniques towards identifying therapeutic targets for COVID-19. Furthermore, in-silico molecular docking approaches to streamline potential drug candidates are also discussed.
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Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared, and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness, and wrinkles. Besides these, skin microbiota is also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well‐known antioxidants, namely vitamin C, resveratrol, and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress‐induced skin pigmentation and aging.
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Background Melasma is a common acquired symmetrically distributed hyperpigmented macules of sun-exposed skin. Skin microneedling acts as a transdermal delivery system that facilitates the penetration of lightening agents to deeper layers of skin. Objective Clinical and dermoscopic evaluation of the efficacy and safety of topical tranexamic acid versus topical vitamin C after microneedling for melasma treatment. Patients and Methods Twenty patients with facial melasma were enrolled in a split-face prospective, randomized uncontrolled study. The right side of the face was treated with topical tranexamic acid after dermapen microneedling, while the left side of the face was treated with topical vitamin C after dermapen microneedling. Sessions were done every 2 weeks for 6 sessions. The Hemi-MASI score and dermoscopic examination before and after treatment were done. Results Hemi-MASI score was reduced after treatment on both sides of the face, besides improvement of the pigmented lesions showed by dermoscopy on both sides and improvement of the vascular component on the tranexamic acid treated side. Conclusion Topical tranexamic acid or vitamin C application after dermapen microneedling was an effective and safe technique in melasma treatment with minimal side effects, and vascular component improvement by tranexamic acid.
Article
Photoaging is a complex process of skin changes associated with chronic ultraviolet exposure. Prevention with photoprotection and treatment with topical retinoids are the core components of a topical antiaging regimen. Other topicals such as hydroquinone, vitamin C, niacinamide, and alpha hydroxyl acid can be added based on specific concerns. However, caution must be used with some of these products as the stability and absorption are major considerations. A simple topical regimen will reduce irritability and enhance compliance.
Article
Melasma is a common disorder of hyperpigmentation that affects populations globally and can adversely affect quality of life. Topical therapies—including hydroquinone and nonhydroquinone‐containing formulations—play a central role in the management of melasma. A literature review was conducted using PubMed and Google Scholar. Search keywords included a combination of the following: “melasma,” “chloasma,” and “topical treatment.” We identified and included seminal and high‐quality peer‐reviewed publications, systematic reviews, randomized controlled trials, case series, case reports, consensus statements, and expert opinions. Topical therapies are widely used for the treatment of melasma. Triple combination cream containing hydroquinone, fluocinolone, and tretinoin is the most studied formulation with the strongest evidence among treatment options. Numerous other prescription‐based and nonprescription topical agents, including a growing list of cosmeceuticals, have been used in the treatment of melasma, albeit in smaller studies. A growing range of topical agents is available for the treatment of melasma. While larger, more robust studies are warranted, nonhydroquinone cosmeceuticals may be useful adjuncts or alternatives to the gold standard of triple‐combination hydroquinone cream.
Article
Oxidative stress is an integral element that influences a variety of biochemical reactions throughout the body and is known to play a notable role in melanogenesis. Exogenous triggers of oxidative stress, such as ultraviolet radiation (UVR) and visible light (VL), lead to pigment formation through somewhat different pathways, but both share a common endpoint – the potential to generate cosmetically undesirable hyperpigmentation. Though organic and inorganic sunscreens are available to protect against the UVR portion of the electromagnetic spectrum, coverage is lacking to protect against the VL spectrum. In this manuscript, we review the phases of tanning, pathways of melanogenesis triggered by UVR and VL, and the associated impact of oxidative stress. We also discuss the known intrinsic mechanisms and paracrine regulation of melanocytes that influence their response to UVR. Understanding these mechanisms and their role in UVR induced hyperpigmentation should potentially lead to identification of useful targets that can be coupled with antioxidant therapy to alleviate this effect. This article is protected by copyright. All rights reserved.
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Background: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults. Objective: This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir. Methods: L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery. Results: L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. Conclusions: Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.
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Vitamin C is known to both inhibit melanin formation and reduce oxidized melanin. However, vitamin C does not easily penetrate the skin. In this study, vitamin C iontophoresis was employed in order to enhance vitamin C penetration. The purpose of this study was to evaluate the efficacy of vitamin C iontophoresis for melasma patients. Twenty-nine females with melasma were enrolled. For iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control. The L (luminance) value was measured by a colorimeter to obtain an objective pigmentation parameter. Twelve weeks after iontophoresis, the colorimeter of the treated site showed a significant decrease in the L value (from 4.60 to 2.78, p = 0.002), compared to that of the control site (from 4.45 to 3.87, p = 0.142). Vitamin C iontophoresis may be an effective treatment modality for melasma.
Article
An inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG, a stable derivative of ascorbic acid) on melanogenesis has been described. Furthermore, glabridin in licorice is known to have inhibitory effects on melanogenesis and widely used for raw materials for depigmenting agents.
Article
Background : An inhibitory effect of ascorbic acid(AsA) on melanogenesis has been described. Iontophoresis is emerging technologies capable of enhancing drug penetration through stratum corneum, the principal barrier to percutaneous absorption. Objective : Our purpose of this study was to evaluate the efficacy of vitamin C-iontophoresis in patients of melasma. Methods : The treatment was performed twice weekly in 15 volunteer patients for a period of 6 weeks by application of vitamin C under a constant direct current of 0.4-0.8 Å for 15minutes. Clinical evaluations using the Melasma Area and Severity Index(MASI) and bioengineering measurement using Chromameter CR 300® were taken before and after treatment. Results : Decreased MASI and light reflectance were noted at the end of 6 weeks, significant clinical improvement in the melasma was seen compared to before treatment. Conclusion : Vitamin C-iontophoresis is an effective, noninvasive treatment of melasma without significant side-effects.
Article
Background and Design: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. Results: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild ''retinoid dermatitis'' occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution. Conclusions: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.
Article
Background and Design: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. Results: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild ''retinoid dermatitis'' occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution.Conclusions: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.(Arch Dermatol. 1994;130:727-733)
Article
Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.
Article
Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with benzyaldehyde. It has been found that the antioxidant activity of SBA is more stable and has a longer lifetime in living cells and organs than Asc. In this study, we investigated the effect of SBA on the induction of melanin in cultured melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was significantly increased by UV-A irradiation. The induction was abolished by mannitol and particularly by superoxide dismutase, suggesting the involvement of O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized by the fact that the induction was also observed in B-16 cells treated with superoxide anion radicals chemically generated in the hypoxanthine/xanthine oxidase-reaction system, instead of UV-A irradiation. The induction of melanin caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To elucidate the mechanism of this suppressive effect, the scavenging activity against O2-, and the inhibitory effect of SBA on tyrosinase activity were examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and the presence of SBA in the medium remarkably inhibited the tyrosinase activity in cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen species (ROS) generated by UV-A irradiation via tyrosinase.
Article
An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. VC-PMG is effective in reducing skin hyperpigmentation in some patients.
Article
The in vitro percutaneous fluxes of propylene glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide (DI) were determined and their effect on nifedipine (N) flux and lag time evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured in vitro by beta-scintigraphy and N permeation was measured by HPLC under finite and infinite dose conditions. Evaluation of each of the solvents separately showed that pure DI possessed the inherent ability to traverse the skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and 40% of the DI had permeated across the skin with nearly linear permeation between 4 and 18 h and the relative order of permeation was PG > DI > N. DI permeation was further aided in the presence of PG and OA. N flux was dependent on concomitant solvent permeation. Over a 24-h test period a dose dependent response was observed for N, with 4.9-15.6 mg of N delivered from the lowest and highest doses, respectively, and the highest dose yielding zero-order flux of 146 (g/h per cm2).
Article
Ultraviolet (UV) irradiation is a major source of environmental damage to skin. Melanin pigmentation protects against this damage by absorbing UV photons and UV-generated free radicals before they can react with DNA and other critical cellular components; and UV-induced melanogenesis or tanning is widely recognized as exposed skin's major defense against further UV damage. This simple-article reviews extensive data suggesting DNA damage or DNA repair intermediates directly triggers tanning and other photoprotective responses. Evidence includes the observations that tanning is enhanced in cultured pigment cells by accelerating repair of UV-induced cyclo-butane pyrimidine dimers or by treating the cells with UV-mimetic DNA-damaging chemicals. Moreover, small single stranded DNA fragments such as thymidine dinucleotides (pTpT), the substrate for almost all DNA photoproducts, also stimulates tanning when added to cultured pigment cells or applied topically to intact skin. In bacteria, single stranded DNA generated by DNA damage or its repair activates a protease that in turn de-represses over 20 genes whose protein products enhance DNA repair and otherwise promote cell survival, a phenomenon termed the SOS response. Interestingly, pTpT also enhances repair of UV-induced DNA damage in human cells and animal skin, at least in part by activating the tumor suppressor protein and transcription factor p53 and thus upregulating a variety of gene products involved in DNA repair and cell cycle regulation. Together, these data suggest that human cells have an evolutionarily conserved SOS-like response in which UV-induced DNA damage serves as signal to induce photoprotective responses such as tanning and increased DNA repair capacity. The responses can also be triggered in the absence of DNA damage by addition of small single-stranded DNA fragments such as pTpT.
Article
So-called darkened age spots encompass distinct pathological processes. The efficacy of topical depigmenting agents is difficult to objectivate. To assess the hypopigmenting effect of three cosmetic formulations using objective biometrological methods. 50 women of South-East Asian ancestry were enrolled in this pilot study. They had solar lentigines according to dermoscopic criteria. The lesions were treated by topical hypopigmenting formulations. Products were applied twice daily for 2 or 3 months. Assessments at 1-month intervals were made using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection and photodensitometry- and image-analysis-assisted corneomelametry. A 20% azelaic acid formulation and another one containing 5% ascorbyl glucosamine, 1% kojic acid and alpha-hydroxyacid esters appeared inefficacious on solar lentigines. A stabilized soy extract showed a better although modest lightening effect when assessed by corneomelametry. The subclinical or faint mottled skin revealed by ultraviolet light examination better responded (p < 0.05) to treatments. Focal epidermal hyperpigmentation is better controlled by topical whitening agents when the increase in melanin content reflects a modest functional hyperactivity of melanocytes.
Article
Melanogenesis is based on the enzymatic conversion of the amino acid tyrosine, through a series of intermediates, to melanin pigments. The nature of the enzymes involved in the different steps of melanogenesis has been intensely debated. However, it is now believed that tyrosinase is responsible for the conversion of tyrosine to dopa and of dopa to dopaquinone, and that peroxidase accomplishes the oxidative polymerization of the eventually formed indoles to eumelanin pigments. Some very few investigators have also considered a main role for peroxidase in initiating melanogenesis. At present, most different hypotheses are focused on tyrosinase-mediated mechanisms to elucidate the melanocytotoxic and depigmenting activities of chemicals. However, many properties of these agents cannot be explained by such mechanisms. Most of the melanocytotoxic agents (e.g. hydroquinone, catechols, butylated hydroxyanisole) can be converted to cytotoxic species, such as quinones, by the peroxidase-H(2)O(2) system. On the other hand, many of the melanogenesis inhibitors which are not known to inhibit tyrosinase (e.g. glucocorticoids, ascorbic acid, indomethacin) have the capacity to strongly inhibit peroxidase activity. We have proposed that peroxidase-mediated mechanisms, in addition to or in several instances rather than tyrosinase-mediated mechanisms, can explain the melanocytotoxic and depigmenting properties of such agents.
Article
Melasma, also known as mask of pregnancy, is a common, acquired hypermelanosis seen in women with Fitzpatrick skin types II-V, and is often recalcitrant to treatment with depigmentation agents. Glycolic acid has been added to hydroquinone formulations in the past to enhance their depigmentation effects, but may cause irritation, leading to postinflammatory hyperpigmentation. To assess the safety and efficacy of a cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen (Glyquin, ICN Pharmaceuticals, Costa Mesa, USA) vs. a cream containing sunscreen alone in the depigmentation of epidermal melasma of the face. Thirty-nine Hispanic women, Fitzpatrick skin types III-V, with bilateral epidermal melasma were enrolled in a randomized controlled trial lasting 12 weeks. Patients underwent twice-daily full-face application with the study cream or with the cream containing sunscreen only. Changes in pigmentation were measured using a mexameter, the melasma area and severity index (MASI), and a global evaluation by the patient and blind investigator. Safety evaluations were performed at each follow-up visit. Thirty-five patients completed the trial. Irritation was more common with the study cream, but resolved with temporary cessation of cream application and the addition of moisturizers. Mexameter results demonstrated a significant decrease in the degree of pigmentation using the study cream compared with the cream containing sunscreen alone (P < 0.0001). Fifteen of 20 patients (75%) using the study cream improved, whereas only two of 15 patients (13%) improved using sunscreen alone. A cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen is safe and effective in the treatment of melasma.
Article
N-Methyl-2-pyrrolidone (NMP) increased the skin permeation of estradiol (E2) in Yucatan micropig epidermis using a modified Franz-type diffusion cell. The addition of NMP significantly increased the fluxes of E2 from water and soybean oil. The flux and skin concentration of E2 were higher from soybean oil than from water and increased with increasing NMP concentrations in soybean oil. Correlation was observed with E2 flux and skin concentration (R(2) = 0.804) NMP enhanced E2 skin permeation because NMP made E2 skin concentration higher. Thus, NMP (10%) was added to the oily gel made by isocetyl isostearate and hydrogenated phospholipid. E2 permeation from the gel without NMP was the same as that from soybean oil suspension. The flux of E2 from the gel with NMP was 0.6 microg/h per cm(2) and might be sufficient for estrogen replacement therapy.
Article
We present here a new cosmetic formula system containing 3% ascorbic acid based on an optimized oil-in-water (O/W) emulsion. This formulation demonstrated a good long-term stability of the active ingredient and also of the emulsion itself. It could be deduced from in vitro release studies that this O/W emulsion enabled a better release of the hydrophilic active agent than an alternative W/O emulsion. By measuring the ultraweak photon emission, which is a well-established parameter for the oxidative stress in the skin, the high in vivo antioxidant capacity of 3% ascorbic acid was demonstrated after 1 week of product application. This placebo-controlled study also proved that ascorbic acid in an O/W cream reduced oxidative stress in human skin significantly better than the derivative sodium ascorbyl-2-phosphate, a more stable vitamin C replacement commonly used in cosmetic formulations. With increasing age, the number of papillae in the epidermal-dermal junction zone in human skin are reduced. This implies a possible consequence of reduced mechanical resistance of the skin and impaired supply of the epidermis with nutrients. In a 1-month placebo-controlled study on 25 human volunteers, a significant increase in the number of dermal papillae after application of the 3% ascorbic acid cream was demonstrated, using a confocal laser scanning microscope. Fine lines and wrinkles are a characteristic sign of aged and especially photo-aged skin. Application of 3% ascorbic acid in a 12-week placebo-controlled usage study indicated a significant reduction of facial wrinkles. Altogether, 3% ascorbic acid in a cosmetic O/W emulsion has been shown to be appropriately stable and to enable a good release of the active agent in vitro as a precondition for a high efficacy in vivo. Application in vivo resulted in a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin. These results were received within a relatively short period of time of product application.
Article
In the present study, we investigated the effects of tomato extract (TE) containing lycopene and palm fruit extract (PE) rich in carotenoids on the growth and pigmentation of melanocyte cultures of Caucasian origin. The extracts were tested at different concentrations and in combination with vitamins E and C. Melanocytes with basic and increased (tyrosine-induced) pigmentation were treated in short-term and long-term experiments. Prevention of UVA-induced DNA damage was studied by using the comet assay. Melanocytes with stimulated melanin production showed reduced growth. Incubation of the cells with TE/PE (20/4 microg/ml) in combination with 35 microM vitamin E and 100 microM vitamin C (COMB 20/4) reduced this growth inhibition, especially in the long-term cultures. Increased production of melanin pigment was obtained when the cells were treated with 2.5 x and 10 x higher concentrations of the TE/PE and the same concentration of vitamins E and C (COMB 50/10 and 200/40). Reduced DNA damage was found after UVA irradiation in cells preincubated with COMB 50/10. The results indicate that the presence of carotenoids from TE and PE in combination with vitamins E and C may influence growth and pigmentation in melanocyte monocultures. Depending on the concentration of the carotenoid mixtures, their presence may provide some protection against the melanogenic intermediates and/or exogenous DNA damage.
Article
Two double-blind studies versus vehicle were carried out to investigate the effects of a topically applied retinol plus vitamin C combination on epidermal and dermal compartments of aged or photoaged human skin. The two studies were performed on postmenopausal women who were selected for treatment based on the mild level of elastosis of their facial skin. At completion of treatment, skin biopsies were collected and processed for classical histology and immunohistochemistry. In the first study (aged skin), 8 volunteers applied the retinol- and vitamin C-containing preparation on the ventral side of one elbow and the vehicle on the other elbow twice daily for 3 months. After the 3-month treatment we observed histological changes mainly within the epidermis. The stratum corneum was thinner with a compact pattern, whereas the epidermal proliferation increased, resulting in a thickening of the viable epidermis. Moreover, the interdigitation index was increased. In the second study (photoaged skin), 11 volunteers were divided in two groups; one applied the retinol- and vitamin C-containing preparation and the other one the vehicle on their face twice daily for 6 months. Facial skin samples presented histologic hallmarks of photoaging, i.e. accumulation of elastotic material in the papillary dermis. After the 6-month topical treatment, the observed histological changes were mainly concentrated at the dermal level. Both treated and control groups showed the same distribution pattern of type I procollagen, however, the high level of type III procollagen originally observed in photoaged skin was reduced in the retinol- and vitamin C-treated group, resulting in a lower type III-to-type I procollagen ratio. Furthermore, a wide band of eosinophilic material just beneath the epidermis, devoid of oxytalan fibers and forming the 'grenz zone', appeared more frequently and was larger in the retinol- and vitamin C-treated group. In conclusion, our results show that repeated topical application of a preparation containing both retinol and vitamin C is able to reverse, at least in part, skin changes induced by both chronologic aging and photoaging.