Supramolecular Salicylic Acid Alleviates Skin Photoaging by Increasing Collagen Density and Elasticity.

BACKGROUND: Skin rejuvenation has always been of great concern. Although salicylic acid (SA) has multiple properties, it is mainly used in dermatology as a superficial peeling agent that can improve photodamaged epidermis. However, the effect of SA on the photoaging dermis is unclear. PURPOSE: To evaluate the efficacy and safety of supramolecular SA alone for treating photoaged skin, and the effect of SSA on photoaged dermis. METHODS: This is a double-blind, randomized, placebo-controlled trial. 36 patients with photodamaged hands were enrolled. One hand was randomly selected as SSA treated side. 30% SSA biweekly and 2% SSA daily was applied for 4 months; an additional follow-up was performed 2 weeks after the last treatment. Skin photoaging score (SPS), global aesthetic improvement scale (GAIS), viscoelasticity, ultrasound parameters, color and transepidermal water loss (TEWL) were assessed. RESULTS: SSA treatment induced a significant increase in collagen density and skin elasticity, accompanied by an increase in dermal thickness and a decrease in melanin index and TEWL. As result, the GAIS and the SPS were improved significantly after SSA treatment. No adverse events were observed after SSA treatments, and 98% of the subjects were satisfied or very satisfied with the treatment. CONCLUSION: SSA can increase collagen density and skin elasticity to alleviate skin photoaging effectively and safely. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Combining superpulse dynamic CO2 laser and supramolecular salicylic acid in the treatment of dense comedones with higher clearance in a shorter time: A prospective, randomized, split-face clinical trial.

OBJECTIVES: Dense comedones are common in patients with acne vulgaris, and promoting treatment can prevent the progression of acne lesions. However, the efficacy-time conflict makes the treatment challenging and the medication options are limited by the side effects. MATERIALS AND METHODS: Thirty-five patients with symmetrical dense comedones were enrolled and the two sides of the face were randomly assigned to receive 30% supramolecular salicylic acid (SSA) combined with CO2 laser or CO2 laser monotherapy at an interval of 2 weeks for six treatment sessions. Comedones count, porphyrin index (PI), texture index (TI), melanin index, erythema index, hydration index (HI), transepidermal water loss (TEWL), and side effects were recorded at each visit till the 12th week. RESULTS: Thirty-one patients completed the study. Comedones on the combined-SSA side were reduced more after six treatments, that the mean reduction rate of the combined-SSA side was 85.76%, and that of the CO2 laser-treated side was 62.32% (Pbetween < 0.001). Combining SSA also showed a better effect on reducing PI and TI than CO2 laser singly (Pbetween < 0.001). TEWL and HI between the two sides showed no significant differences after treatments. No permanent or severe side effects were observed on both side. CONCLUSIONS: The treatment combined CO2 laser with 30% SSA dealt with the efficacy-time conflict while significantly reducing comedones and improving skin texture in 12 weeks and no serious adverse reactions occurred. LIMITATIONS: It is a single-center study and the number of subjects was small.

Evaluation of 30% supramolecular salicylic acid followed by 1565-nm non-ablative fractional laser on facial acne and subsequent enlarged pores.

The treatment of acne vulgaris and enlarged pore remains challenging. The 30% supramolecular salicylic acid (SSA) is a newly developed form of SA which affects pathogenic factors of acne. Non-ablative fractional laser (NAFL) promotes remodeling and decreases sebum excretion with minimal side effect. The current study was aimed to evaluate the sequential modality with 30% SSA followed by 1565-nm NAFL on facial acne and subsequent enlarged pores. A 20-week-duration prospective study was performed. Consecutive 4 sessions of 30% SSA treatment were conducted, at 2-week intervals. Two weeks after the last session of 30% SSA, 3 sessions of 1565-nm NAFL treatment were applied, at 4-week intervals. The noninvasive devices measured scores of red areas and pores, cuticle moisture, and sebum secretion. The main subjective evaluation was global acne grading system (GAGS). The side effects were recorded. Compared to baseline, the scores of red areas and pores, sebum secretion, and GAGS significantly decreased after series sessions of 30% SSA treatments (P < 0.05). The sequential application of 1565-nm NAFL maintained the good results (P < 0.05, comparing to baseline) and even further decreased the sebum secretion (P < 0.05, comparing to SSA). The cuticle moisture remained unchanged during whole period, and side effects including tingling sensation, pain, erythema, and edema were quickly reversible and acceptable. The significant improvements of acne and pores were produced by 30% SSA, and 1565-nm NAFL inhibited the sebum secretion and maintained the efficacies of 30% SSA. The sequential modality of 30% SSA followed by 1565-nm NAFL was an alternative choice for acne vulgaris companied with enlarged pores.

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized, split-face, open-label, single-center study.

BACKGROUND: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme. OBJECTIVES: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne. MATERIALS AND METHODS: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28 days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time. RESULTS: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p > 0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p > 0.05). CONCLUSION: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Clinical efficacy of 595 nm pulsed dye laser in combination with supramolecular salicylic acid in the treatment of rosacea.

OBJECTIVE: This research was aimed at ascertaining the clinical effects of 595 nm pulsed dye laser (PDL) in combination with supramolecular salicylic acid (SSA) in the treatment of rosacea. METHODS: Eighty-four patients with rosacea were selected, of which 42 patients treated with PDL alone were considered as the control group, and 42 patients treated with 595 nm PDL in combination with 30% SSA were regarded as the observation group. The treatment continued for 4 months in the two groups. Clinical symptom scores, skin barrier function indicators, serum inflammatory factors, Acne⁃QOL scores and adverse reactions between the two groups were compared. RESULTS: After treatment, levels of inflammatory factors, clinical symptom scores, transdermal water loss, and oil volume were decreased, and epidermal water content and Acne-QOL scores were increased in both groups (all P < 0.05), and the changes in the observation group were more pronounced versus the control group (all P < 0.05). The difference in the incidence of adverse reactions was not statistically significant between the two groups (P > 0.05). CONCLUSION: 595 nm PDL in combination with SSA is safe in the treatment of rosacea.

Supramolecular salicylic acid ameliorates rosacea-like eruptions by suppressing NLRP3-mediated inflammasome activation in mice.

BACKGROUND: Rosacea is a chronic inflammatory skin disease with immunological dysfunction. Supramolecular salicylic acid (SSA) has the properties of keratolytic, antibacterial, and anti-inflammatory. However, the mechanism of SSA in the treatment of rosacea is still unclear. OBJECTIVE: To investigate the efficiencies and molecular mechanisms of SSA in rosacea. METHODS: Forty mice were randomly divided into four groups (10 in each group): control, LL-37, LL-37 + azelaic acid (AzA), and LL-37 + SSA. Forty µl LL-37 (320 µM) was administered intradermally into the dorsal skin of the mice in the latter 3 groups every 12 h and 4 times altogether (0 h, 12 h, 24 h, 36 h). Twenty % AzA was applied on the eruptions after the first and third LL-37 injection (0 h, 24 h) in LL-37 + AzA group, while 30 % SSA was applied after the first injection (0 h) in LL-37 + SSA group. The redness score and redness area were evaluated. The skin barrier function was measured by the transepidermal water loss (TEWL) and pH. The infiltration of inflammatory cells was evaluated by hematoxylin-eosin staining, and the inflammatory biomarkers were analyzed by RT-PCR and immunohistochemistry. RESULTS: SSA alleviated LL-37-induced rosacea-like inflammation. The increased TEWL and pH induced by LL-37 were also reversed by SSA. In addition, SSA reduced inflammatory cell infiltration and suppressed the production of Toll-like receptor 2, Matrix metallopeptidase 9, kallikrein 5, LL-37 associated with rosacea, and inhibited LL-37-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3)-mediated inflammasome activation in mice. CONCLUSIONS: Our findings indicated that SSA ameliorated LL-37-induced rosacea-like lesions by suppressing NLRP3-mediated inflammasome activation in mice.

Effect of 30% Supramolecular Salicylic Acid Peel on Skin Microbiota and Inflammation in Patients with Moderate-to-Severe Acne Vulgaris.

INTRODUCTION: Thirty-percent supramolecular salicylic acid (SSA), a modified salicylic acid preparation, is a safe and effective treatment for moderate-to-severe acne vulgaris (AV). However, its mechanism of action remains unclear. We aimed to analyze the role of 30% SSA peels on skin microbiota and inflammation in patients with moderate-to-severe AV. METHODS: A total of 28 patients were enrolled and received 30% SSA peels biweekly for 2 months. The Global Acne Grading System (GAGS) score, skin water content, transepidermal water loss (TEWL), pH, and sebum levels were assessed. Skin microbial samples and perilesional skin biopsies were obtained at the onset and 2 weeks after treatment completion. Samples were characterized using a high-throughput sequencing approach targeting a portion of the bacterial 16S ribosomal RNA gene. RESULTS: After treatment, patients showed a significant improvement in their GAGS score and skin barrier indicators (P < 0.05). The GAGS score was positively associated with both the sebum concentration (R = 0.3, P = 0.027) and pH (R = 0.39, P = 0.003). Increased expression of caveolin-1 and decreased expression of interleukin (IL)-1a, IL-6, IL-17, transforming growth factor beta, and toll-like receptor 2 were observed in the skin tissue after treatment. The richness and evenness of the cutaneous microbiome decreased after treatment and the Staphylococcus proportion decreased significantly (P < 0.05), whereas the Propionibacterium proportion tended to decrease (P = 0.066). CONCLUSIONS: On the basis of analyses of the skin barrier and microbiota, we speculate that the 30% SSA peel may have a therapeutic effect in patients with moderate-to-severe AV by improving the skin microenvironment and modulating the skin microbiome, thus reducing local inflammation.

Stabilization of Acne Vulgaris-Associated Microbial Dysbiosis with 2% Supramolecular Salicylic Acid.

Facial microbiota dysbiosis is an important factor in causing acne vulgaris. The present study aimed to analyze the effect of 2% Supramolecular Salicylic Acid (SSA) on acne-associated facial bacteria. In the current study, 30 acne vulgaris patients (treated with 2% SSA for eight weeks) and ten volunteers with no facial acne were selected. Samples from acne patients (before and after treatment) and volunteers (not treated) were analyzed via high throughput sequencing, Deblur algorithm, and R microbiome package. After treatment with 2% SSA, the total lesion count and global acne grading system (GAGS) score reduced significantly (p < 0.001). Metagenomic sequencing analysis revealed that the pre-treated acne group had low α and deviated ß diversity compared to the control and post-treated acne groups. Due to the treatment with 2% SSA, α diversity index was increased and ß diversity was stabilized significantly (p < 0.001). The relative abundance of bacterial genera in the pre-treated acne group was uneven and had a high proportion of Staphylococcus, Ralstonia, and Streptococcus. The proportion of these three genera was significantly decreased in the post-treated group, and overall bacteria genera distribution tends toward the healthy individual. It is concluded that 2% SSA normalizes the microbial communities associated with the skin.

0.5-5% Supramolecular Salicylic Acid Hydrogel is Safe for Long-Term Topical Application and Improves the Expression of Genes Related to Skin Barrier Homeostasis in Mice Models.

Background: As a keratolytic, salicylic acid (SA) can be topically applied in various formulations and doses in dermatology. Supramolecular SA hydrogel, a new SA formulation with higher bioavailability, is developed and commercially available nowadays. However, there still remain concerns that the long-term and continual application of SA at low concentrations may jeopardize the cutaneous barrier properties. Aim of the Study: To reveal the long-term effects of 0.5-5% supramolecular SA hydrogel on the skin barrier in normal mice models. Materials and Methods: The 0.5%, 1%, 2%, and 5% supramolecular SA hydrogel or hydrogel vehicle without SA was applied to mice's shaved dorsal skin once per day respectively. Tissue samples of the dorsal skin were harvested on day 14 and 28 of the serial application of SA for histopathological observation and transcriptomic analysis. Results: Following topical supramolecular SA hydrogel therapy with various concentrations of SA (0.5%, 1%, 2%, and 5%) for 14 days and 28 days, there were no obvious macroscopic signs of impaired cutaneous health and no inflammatory or degenerative abnormalities were observed in histological results. Additionally, the transcriptomic analysis revealed that on day 14, SA dramatically altered the expression of genes related to the extracellular matrix structural constituent. And on day 28, SA regulated gene expression profiles of keratinization, cornified envelope, and lipid metabolism remarkably. Furthermore, the expression of skin barrier related genes was significantly elevated after the application of SA based on RNA-seq results, and this is likely to be associated with the PPAR signaling pathway according to the enrichment analysis. Conclusion: Our findings demonstrated that the sustained topical administration of the 0.5-5% supramolecular SA hydrogel for up to 28 days did no harm to normal murine skin and upregulated the expression of genes related to the epidermal barrier.

Assessment of the Efficacy and Safety of 30% Supramolecular Salicylic Acid Peeling for Papulopustular Rosacea Treatment.

Background: Thirty per cent supramolecular salicylic acid (SSA) is a water-soluble, sustained release salicylic acid (SA) modality, which is well tolerated by sensitive skin. Anti-inflammatory therapy plays an important role in papulopustular rosacea (PPR) treatment. SSA at a 30% concentration has a natural antiinflammatory property. Aims: This study aims to investigate the efficacy and safety of 30% SSA peeling for PPR treatment. Methods: Sixty PPR patients were randomly divided into two groups: SSA group (30 cases) and control group (30 cases). Patients of the SSA group were treated with 30% SSA peeling three times every 3 weeks. Patients in both groups were instructed to topically apply 0.75% metronidazole gel twice daily. Transdermal water loss (TEWL), skin hydration and erythema index were assessed after 9 weeks. Results: Fifty-eight patients completed the study. The improvement of erythema index in the SSA group was significantly better than that in the control group. No significant difference was found in terms of TEWL between the two groups. The content of skin hydration in both the groups increased, but there was no statistical significance. No severe adverse events were observed in both the groups. Conclusion: SSA can significantly improve the erythema index and overall appearance of skin in rosacea patients. It has a good therapeutic effect, good tolerance and high safety.

Clinical study on treatment of facial seborrheic dermatitis with intense pulsed light combined with 30% supramolecular salicylic acid

OBJECTIVES: In this study, we investigated the effects of intense pulsed light (IPL) combined with 30% supramolecular salicylic acid on facial seborrheic dermatitis. METHODS: A total of 45 patients with mild or moderate facial seborrheic dermatitis were selected from our hospital between September 2018 and September 2019. The patients were divided into three groups consisting of 15 patients each. The first group was exposed to a combination of IPL and 30% supramolecular salicylic acid treatment, the second group was exposed to the IPL treatment alone, and the third group was exposed to the 30% supramolecular salicylic acid treatment alone. They were treated once every 4 weeks in three consecutive rounds. RESULTS: Facial lesions and symptoms were observed 4 and 12 weeks after the first treatment, and adverse reactions were recorded. The combination group showed significant improvement in symptoms 4 weeks after the first treatment, while the individual treatment groups showed no significant improvement. After three rounds of treatments, seborrheic dermatitis had significantly decreased in the three groups; the efficacy of the combined treatment group was significantly higher than that of the IPL group and the 30% supramolecular salicylic acid group. CONCLUSION: IPL combined with 30% supramolecular salicylic acid was effective in the treatment of facial seborrheic dermatitis and provided a quicker result with no adverse reactions.