Emerging topical treatments for psoriasis

Kivelevitch, Darío; Hebeler, Katherine R.; Patel, Mahir; Menter, Alan

doi:10.1517/14728214.2013.861418

Cited by 17 publications

(16 citation statements)

References 33 publications

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“…) of Foxp3+ regulatory T cells, suppressing skin inflammation (Kivelevitch et al. ) and improving epidermal integrity compromised by tape stripping (Hong et al. ).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

et al. 2017

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In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset. Female BALB/c dams were fed a vitamin D3‐supplemented (2280 IU/kg, VitD+) or nonsupplemented (0 IU/kg, VitD−) diet from 3 weeks of age, and mated at 8 weeks of age. Male offspring were fed the same diet as their mother. Some offspring initially fed the VitD− diet were switched to a VitD+ diet from 8 weeks of age (VitD−/+). At 12 weeks of age, signs of low‐level inflammation were observed in the bronchoalveolar lavage fluid (BALF) of VitD− mice (more macrophages and neutrophils), which were suppressed by subsequent supplementation with vitamin D3. There was no difference in the level of expression of the tight junction proteins occludin or claudin‐1 in lung epithelial cells of VitD+ mice compared to VitD− mice; however, claudin‐1 levels were reduced when initially vitamin D‐deficient mice were fed the vitamin D3‐containing diet (VitD−/+). Reduced total IgM levels were detected in BALF and serum of VitD−/+ mice compared to VitD+ mice. Lung mRNA levels of the vitamin D receptor (VDR) were greatest in VitD−/+ mice. Total IgG levels in BALF were greater in mice fed the vitamin D3‐containing diet, which may be explained by increased activation of B cells in airway‐draining lymph nodes. These findings suggest that supplementation of initially vitamin D‐deficient mice with vitamin D3 suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs.

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“…) of Foxp3+ regulatory T cells, suppressing skin inflammation (Kivelevitch et al. ) and improving epidermal integrity compromised by tape stripping (Hong et al. ).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

et al. 2017

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“…Psoriasis treatment includes topical therapy, systemic therapy, phototherapy, and biological therapy. However, topical therapy is mostly preferred for mild to moderate psoriasis in which corticosteroids, vitamin D analogues, vitamin A retinoids are used as monotherapy or in combination . As a part of combination therapy, betamethasone valerate and tazarotene are preferred to provide improved therapeutic efficacy with lesser side effects .…”

Section: Introductionmentioning

confidence: 99%

Stability indicating liquid chromatographic method for simultaneous quantification of betamethasone valerate and tazarotene in in vitro and ex vivo studies of complex nanoformulation

Rapalli

Singhvi

Gorantla

et al. 2019

J of Separation Science

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Low‐potency corticosteroid betamethasone valerate and vitamin‐A tazarotene are used in combination for effective treatment of psoriasis. There is no robust high‐performance liquid chromatography analytical technique available for simultaneous estimation of betamethasone valerate and tazarotene in conventional and nanocarriers based formulations. A simple, accurate, robust isocratic high‐performance liquid chromatography method was developed for simultaneous estimation of betamethasone valerate and tazarotene in topical pharmaceutical formulations. The developed method was validated as per the regulatory guidelines. The validated method was linear over the concentration range of 150–6000 ng/mL (r2 > 0.999) at 239 nm wavelength. Limits of detection and quantification of two analytes were 50 and 150 ng/mL, respectively. The %relative standard deviation for intraday and interday precision was less than 2%. The method was also evaluated in the presence of forced degradation conditions. The developed method was successfully applied for in vitro and ex vivo drug release studies of in‐house designed nanoformulations.

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“…Antibodies specific to tumor necrosis factor (TNF)-a, interleukin (IL)-12/23 p40, IL-17, and IL-4 receptor (IL-4R)/ IL-13 receptor (IL-13R) are clinically effective for moderate-to-severe psoriasis or AD (Crow, 2012;Beck et al, 2014;Thaçi et al, 2015). However, the majority of patients with mild-to-moderate disease are treated with topical corticosteroids, calcineurin inhibitors, or vitamin D analogs (Menter et al, 2009;Ring et al, 2012;Kivelevitch et al, 2013). Glucocorticoids induce skin atrophy and suppress the hypothalamic-pituitary-adrenal axis, and these side effects are particularly concerning in children, who comprise the majority of patients with AD (Kivelevitch et al, 2013;Schäkel et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…However, the majority of patients with mild-to-moderate disease are treated with topical corticosteroids, calcineurin inhibitors, or vitamin D analogs (Menter et al, 2009;Ring et al, 2012;Kivelevitch et al, 2013). Glucocorticoids induce skin atrophy and suppress the hypothalamic-pituitary-adrenal axis, and these side effects are particularly concerning in children, who comprise the majority of patients with AD (Kivelevitch et al, 2013;Schäkel et al, 2014). Calcineurin inhibitors have additional potential risks of infection and cancer and have boxed warnings required by the U.S. Food and Drug Administration (Guttman-Yassky et al, 2011b;Ring et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes

Chen¹,

Virtucio²,

Zemska³

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Psoriasis and atopic dermatitis are skin diseases affecting millions of patients. Here, we characterize benzoxaborole phosphodiesterase (PDE)-4 inhibitors, a new topical class that has demonstrated therapeutic benefit for psoriasis and atopic dermatitis in phase 2 or phase 3 studies.are potent PDE4 inhibitors with similar affinity for PDE4 isoforms and equivalent inhibition on the catalytic domain and the full-length enzyme. These benzoxaboroles are less active on other PDE isozymes. Compd4 binds to the catalytic domain of PDE4B2 with the oxaborole group chelating the catalytic bimetal and overlapping with the phosphate in cAMP during substrate hydrolysis, and the interaction extends into the adenine pocket. In cell culture, benzoxaborole PDE4 inhibitors suppress the release of tumor necrosis factor-a, interleukin (IL)-23, IL-17, interferon-g, IL-4, IL-5, IL-13, and IL-22, and these cytokines contribute to the pathologic changes in skin structure and barrier functions as well as immune dysregulation in atopic dermatitis and psoriasis. Treatment with compd3 or N 6 ,29-O-dibutyryladenosine 39,59-cyclic monophosphate increases cAMP response element binding protein phosphorylation in human monocytes and decreases extracellular signal-regulated kinase phosphorylation in human T cells; these changes lead to reduced cytokine production and are among the mechanisms by which compd3 blocks cytokine release. Topical compd3 penetrates the skin and suppresses phorbol myristate acetate-induced IL-13, IL-22, IL-17F, and IL-23 transcription and calcipotriol-induced thymic stromal lymphopoietin expression in mouse skin. Skin thinning is a major dose-limiting side effect of glucocorticoids. By contrast, repeated application of compd3 did not thin mouse skin. These findings show the potential benefits and safety of benzoxaborole PDE4 inhibitors for the treatment of psoriasis and atopic dermatitis.

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Emerging topical treatments for psoriasis

Cited by 17 publications

References 33 publications

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

Stability indicating liquid chromatographic method for simultaneous quantification of betamethasone valerate and tazarotene in in vitro and ex vivo studies of complex nanoformulation

Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes

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