Topical retinoids for acne

Yeh, Lindsey C.; Bonati, Lauren Meshkov; Silverberg, Nanette B.

doi:10.12788/j.sder.2016.024

Cited by 11 publications

(8 citation statements)

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“…All - trans retinoic acid (ATRA), the prototype of topical retinoids, is comedolytic, resolves precursor microcomedones and is anti-inflammatory [ 31 , 32 ]. Topical ATRA has been shown to transform the horn-filled utriculi of the rhino mouse into normal follicles [ 33 ].…”

Section: Retinoic Acidmentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.

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Section: Retinoic Acidmentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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“…Additionally, there is a long history of topical application of RA in dermatology, such as to enhance wound healing, treat acne, and reverse skin aging caused by UV damage. These topical applications have proven relatively safe 10 – 13 . Recently, we have found that in macrophage polarization, a process essential to innate immunity, RA treatment significantly elevates the expression of Arginase 1 (Arg1), a gene product critical to wound healing process.…”

Section: Introductionmentioning

confidence: 99%

Glyburide and retinoic acid synergize to promote wound healing by anti-inflammation and RIP140 degradation

Lin

Liu

Pook

et al. 2018

Sci Rep

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Chronic inflammation underlies the development of metabolic diseases and individuals with metabolic disease often also suffer from delayed wound healing due to prolonged inflammation. Resolving inflammation provides a therapeutic strategy in treating metabolic diseases. We previously showed that during an anti-inflammatory response when macrophages were alternatively (M2) polarized, retinoic acid (RA) dramatically activated arginase 1 gene (Arg1), a gene crucial for wound healing. Here we report that a widely used sulfonylurea drug for type 2 diabetes mellitus (T2DM), glyburide, enhances the anti-inflammatory response and synergizes with RA to promote wound healing. Our data also delineate the mechanism underlying glyburide’s anti-inflammatory effect, which is to stimulate the degradation of a pro-inflammatory regulator, Receptor Interacting Protein 140 (RIP140), by activating Ca2+/calmodulin-dependent protein kinase II (CamKII) that triggers specific ubiquitination of RIP140 for degradation. By stimulating RIP140 degradation, glyburide enhances M2 polarization and anti-inflammation. Using a high-fat diet induced obesity mouse model to monitor wound healing effects, we provide a proof-of-concept for a therapeutic strategy that combining glyburide and RA can significantly improve wound healing. Mechanistically, this study uncovers a new mechanism of action of glyburide and a new pathway modulating RIP140 protein degradation that is mediated by CamKII signaling.

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“…Dosing compliance, defined as participants not missing more than 5 consecutive days of dosing and applying 80-120% of ex-or adapalene 0.1% or 0.3% in treating acne. [9][10][11] While the efficacy and safety of topical retinoids are well established, 12,13 adverse effects such as irritation, erythema, peeling, and dryness can occur in the first weeks of treatment, especially at higher concentrations. 7,12 To address these issues, a new tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] While the efficacy and safety of topical retinoids are well established, 12,13 adverse effects such as irritation, erythema, peeling, and dryness can occur in the first weeks of treatment, especially at higher concentrations. 7,12 To address these issues, a new tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology. 14 An oil-in-water emulsion-structured by a three-dimensional mesh matrix containing tazarotene along with hydrating and moisturizing agents-allows for more uniform release and increased absorption of ingredients.…”

Section: Discussionmentioning

confidence: 99%

Once-Daily Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Sex

Kircik¹,

Gold²,

Beer³

et al. 2020

JDD

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Background: Two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies (NCT03168321 and NCT03168334) demonstrated the efficacy and safety of tazarotene 0.045% lotion in participants with moderate-to-severe acne. Data from these studies were pooled and analyzed post hoc to evaluate outcomes by sex. Methods: Patients aged ≥9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Outcomes comprised inflammatory/noninflammatory lesion counts, treatment success (proportion of participants achieving ≥2-grade reduction from baseline in EGSS and score of 0 ["clear"] or 1 ["almost clear"]), and treatment-emergent adverse events (TEAEs). Results: A total of 1,064 females and 550 males were included in this analysis. For both sexes, least-squares mean percent changes from baseline to week 12 in lesion counts were significantly greater with tazarotene 0.045% lotion versus vehicle (inflammatory: females, -60.1% vs -52.1%; males, -53.6% vs -39.8%; noninflammatory: females, -57.6% vs -44.9%; males, -52.9% vs -36.5%; P<0.001, all). The percentage of participants achieving treatment success at week 12 was also significantly higher with tazarotene 0.045% lotion versus vehicle in females and males (P<0.001, both). Compared with tazarotene-treated males, tazarotene-treated females had significantly greater changes from baseline in inflammatory and noninflammatory lesions and a greater proportion achieved treatment success at week 12 (P<0.05, all). TEAE rates were similar between tazarotene-and vehicle-treated males; rates were higher for tazarotene-treated females than vehicle-treated females. Conclusions: Tazarotene 0.045% lotion was efficacious and well tolerated in the treatment of moderate-to-severe acne in female and male participants.

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Topical retinoids for acne

Cited by 11 publications

References 0 publications

p53: key conductor of all anti-acne therapies

p53: key conductor of all anti-acne therapies

Glyburide and retinoic acid synergize to promote wound healing by anti-inflammation and RIP140 degradation

Once-Daily Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Sex

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