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BACKGROUND: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth. METHODS: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array. RESULTS: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth. CONCLUSIONS: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.
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Supervivencia Celular , Estrés del Retículo Endoplásmico , Regulación Neoplásica de la Expresión Génica , Melanoma , Humanos , Estrés del Retículo Endoplásmico/genética , Estrés del Retículo Endoplásmico/efectos de los fármacos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Muerte Celular/genética , Apoptosis/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/genética , Proliferación Celular/efectos de los fármacos , Proteínas de la MembranaRESUMEN
Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40-70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.
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Nanopartículas , Ácidos Nicotínicos , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Absorción Cutánea , Piel , Ácidos Nicotínicos/administración & dosificación , Ácidos Nicotínicos/química , Ácidos Nicotínicos/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Animales , Porcinos , Nanopartículas/química , Humanos , Absorción Cutánea/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/farmacocinética , Fármacos Dermatológicos/química , Portadores de Fármacos/química , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Liberación de Fármacos , Administración Cutánea , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Acné Vulgar/tratamiento farmacológico , Composición de Medicamentos/métodos , Enfermedades de la Piel/tratamiento farmacológicoRESUMEN
INTRODUCTION: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. METHOD: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. RESULTS: The expert panel reached consensus on 20 statements. CONCLUSION: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.
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This case report describes an 80-year-old man who presented with a growing erythematous nodule with erosion, measuring 0.6 cm × 0.6 cm, on his right temple. This lesion was later diagnosed as atypical fibroxanthoma (AFX). Instead of undergoing Mohs surgery, the gold standard treatment, the patient opted to pursue a topical treatment regimen because of financial costs associated with surgical removal and repair. This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. The patient was directed to use this combination 5 days per week for 6 weeks. The specified dosage for each medication was a fifth of a packet of imiquimod 5% cream, an equivalent amount of tazarotene 0.1% cream, and a single drop of 5-fluorouracil 2% solution. These were combined on a bandage and placed on the lesion overnight. Following the treatment, a 3-week post-application examination revealed an erosion, 1.0 cm × 0.9 cm, amidst erythema. A subsequent incisional biopsy with histopathology and stains for CD10 and CD99, 3 weeks after treatment, and three punch biopsies with histopathology and stains for CD10 and CD99, 1-year post-treatment, confirmed the absence of AFX. AFX is a superficial variant of pleomorphic dermal sarcoma (PDS), which shares histologic similarities, yet the exact relationship between AFX/PDS and undifferentiated pleomorphic sarcoma is still not well understood. Previous studies have indicated a genomic similarity between AFX/PDS and cutaneous squamous cell carcinoma (cSCC), which suggests the potential efficacy of cSCC-targeted treatments for AFX/PDS. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.
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BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.
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Acné Vulgar , Antibacterianos , Peróxido de Benzoílo , Fármacos Dermatológicos , Ácidos Dicarboxílicos , Doxiciclina , Isotretinoína , Ácido Salicílico , Espironolactona , Humanos , Acné Vulgar/tratamiento farmacológico , Isotretinoína/administración & dosificación , Isotretinoína/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Peróxido de Benzoílo/administración & dosificación , Peróxido de Benzoílo/uso terapéutico , Ácidos Dicarboxílicos/administración & dosificación , Ácidos Dicarboxílicos/uso terapéutico , Espironolactona/administración & dosificación , Espironolactona/uso terapéutico , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Ácido Salicílico/administración & dosificación , Ácido Salicílico/uso terapéutico , Medicina Basada en la Evidencia/normas , Administración Oral , Retinoides/administración & dosificación , Retinoides/uso terapéutico , Tetraciclinas/administración & dosificación , Tetraciclinas/uso terapéutico , Adolescente , Minociclina/administración & dosificación , Minociclina/uso terapéutico , Niño , Administración Cutánea , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/uso terapéutico , Quimioterapia Combinada , Femenino , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Inyecciones Intralesiones , Adulto , Cortodoxona/análogos & derivados , PropionatosRESUMEN
Spinal cord injury (SCI) often leads to cell death, vascular disruption, axonal signal interruption, and permanent functional damage. Currently, there are no clearly effective therapeutic options available for SCI. Considering the inhospitable SCI milieu typified by ischemia, hypoxia, and restricted neural regeneration, a novel injectable hydrogel system containing conductive black phosphorus (BP) nanosheets within a lipoic acid-modified chitosan hydrogel matrix (LAMC) is explored. The incorporation of tannic acid (TA)-modified BP nanosheets (BP@TA) into the LAMC hydrogel matrix significantly improved its conductivity. Further, by embedding a bicyclodextrin-conjugated tazarotene drug, the hydrogel showcased amplified angiogenic potential in vitro. In a rat model of complete SCI, implantation of LAMC/BP@TA hydrogel markedly improved the recovery of motor function. Immunofluorescence evaluations confirmed that the composite hydrogel facilitated endogenous angiogenesis and neurogenesis at the injury site. Collectively, this work elucidates an innovative drug-incorporated hydrogel system enriched with BP, underscoring its potential to foster vascular and neural regeneration.
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Hidrogeles , Regeneración Nerviosa , Fósforo , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/fisiopatología , Animales , Hidrogeles/química , Hidrogeles/farmacología , Regeneración Nerviosa/efectos de los fármacos , Fósforo/química , Ratas , Ratas Sprague-Dawley , Nanoestructuras/química , Neovascularización Fisiológica/efectos de los fármacos , InyeccionesRESUMEN
Objective: The objective was to compare the safety and efficacy of noncorticosteroid topical treatments for plaque psoriasis. Data Sources: A literature search of the PubMed database was performed (January 1978 to May 2023) using the keywords plaque psoriasis, tapinarof, benvitimod, Vtama, roflumilast, Zoryve, pimecrolimus, tacrolimus, tazarotene, tacalcitol, calcitriol, Vectical, calcipotriene, Dovonex, tacalcitol, vitamin D analogs, salicylic acid, non-corticosteroid topical, Investigator's Global Assessment, and Physician's Global Assessment. Study Selection and Data Extraction: Relevant English-language articles and clinical trial data were considered. Data Synthesis: Six noncorticosteroid topical classes for the treatment of plaque psoriasis were selected. The percentage of patients with plaque psoriasis who achieved Investigator's Global Assessment (IGA) success after 8 weeks of treatment with tacalcitol, calcipotriene/betamethasone dipropionate compound, tazarotene/halobetasol propionate, and roflumilast was 17.9%, 39.9%, 40.7%, and 42.4%, respectively. For 12-week trials of tapinarof and coal tar, 37.4% and 58.2% of patients achieved IGA success, respectively. There were 48% and 71.4% reductions in IGA scores with salicylic acid (12 weeks) and pimecrolimus (4 weeks), respectively. Finally, 66.7% of patients achieved Physician's Global Assessment success with 8 weeks of tacrolimus. There were no serious adverse events for the noncorticosteroid topicals. Conclusion: Noncorticosteroid topicals are suitable options for patients with plaque psoriasis who would like to avoid topical corticosteroids or have experienced adverse effects from chronic corticosteroid use. Due to treatment duration differences and varied outcome measures, it is unclear which noncorticosteroid topical is most efficacious; however, calcineurin inhibitors appear to exhibit the greatest efficacy. Each topical was efficacious in treating plaque psoriasis and had an adequate safety profile. Despite several treatment options for plaque psoriasis, medication adherence is a limiting factor.
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Dermatological diseases such as atopic dermatitis, acne, and psoriasis result in significant morbidity and decreased quality of life. The first line of treatment for such diseases is often topical medications. While topical delivery allows active drug to be delivered directly to the target site, the skin is a virtually impermeable barrier that impedes delivery of large molecules. Thus, the formulation and delivery system are integral elements of topical medications. Patients also have preferences for the properties of topical formulations and these preferences can positively or negatively impact adherence. Therefore, the choice of topical formulation is a key consideration. Recent developments in drug delivery systems have produced enhanced topical treatments that improve efficacy, safety, and patient acceptability. Awareness of the delivery system in which drugs are formulated is critical as this can have profound implications on treatment success. This paper provides an overview and clinical commentary on advances in topical delivery systems and their impact on dermatological practice.
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Acné Vulgar , Dermatología , Humanos , Sistemas de Liberación de Medicamentos , Calidad de Vida , PielRESUMEN
This study aimed to formulate and optimize an anti-acne drug namely tazarotene (TZR) in essential oil-based microemulsion (ME) using either Jasmine oil (Jas) or Jojoba oil (Joj). TZR-MEs were prepared using two experimental designs (Simplex Lattice Design®) and characterized for droplet size, polydispersity index, and viscosity. Further in vitro, ex vivo, and in vivo investigations were performed for the selected formulations. Results revealed that TZR-selected MEs exhibited suitable droplet size, homogenous dispersions, and acceptable viscosity, in addition to spherical-shaped particles in morphology. The ex vivo skin deposition study showed a significant TZR accumulation in all skin layers for the Jas-selected ME over the Joj one. Further, TZR didn't show any antimicrobial activity against P. acnes, however, it was boosted when it was incorporated into the selected MEs. The in vivo study results of the infected mice ears induced by P. acnes revealed that our selected MEs successfully reached a high level of ear thickness reduction of 67.1% and 47.4% for Jas and Joj selected MEs, respectively, versus only 4% for the market product. Finally, the findings confirmed the ability to use essential oil-based ME, particularly with Jas, as a promising carrier for topical TZR delivery in the treatment of acne vulgaris.
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BACKGROUND/AIM: Currently, there are few drug options available to treat malignant melanoma. Tazarotene-inducible gene 1 (TIG1) was originally isolated from skin tissue, but its function in skin tissue has not been clarified. The aim of this study was to elucidate the effect of TIG1 and mTOR signaling pathways associated with VAC14 on melanoma. MATERIALS AND METHODS: The expression of TIG1 and VAC14 in melanoma tissue was analyzed using a melanoma tissue cDNA array. The interaction between TIG1 and VAC14 was analyzed using immunoprecipitation and immunostaining. Western blot was used to investigate the molecular targets of TIG1 and VAC14 in melanoma cells. RESULTS: TIG1 was highly expressed in normal skin tissue but was low in malignant melanoma, while VAC14 showed the opposite trend. TIG1 inhibited insulin-induced cell proliferation and insulin-activated mammalian target of rapamycin complex 1 (mTORC1)-p70 S6 kinase but did not affect the level of phospho-AKT in A2058 melanoma cells. This suggests that the main target of TIG1 regulating cell growth is phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] rather than the PI(4,5)P2 signaling pathway. Additional TIG1 showed no additive effect on the inhibition of mTOR signaling in the absence of VAC14 expression, suggesting that TIG1 inhibited the activation of mTOR mainly by inhibiting VAC14. CONCLUSION: TIG1 may play an important role in preventing malignant melanoma through retinoic acid via VAC14.
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Melanoma , Proteínas de la Membrana , Humanos , Insulinas , Melanoma/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de la Membrana/genética , Melanoma Cutáneo MalignoAsunto(s)
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoriasis , Humanos , Clobetasol/uso terapéutico , Ácidos Nicotínicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento , Fármacos Dermatológicos/uso terapéutico , Índice de Severidad de la Enfermedad , Administración Cutánea , Método Doble Ciego , Combinación de MedicamentosRESUMEN
BACKGROUND: Irritation with topical retinoids presents a significant impediment to acne treatment adherence. Two studies assessed the irritation potential of tazarotene 0.045% lotion versus adapalene 0.3% gel and trifarotene 0.005% cream. METHODS: In two double-blind, 12-day modified cumulative irritation patch studies, healthy adults (N = 20 each) had two active patches, containing 0.1 cc of tazarotene 0.045% lotion and either adapalene 0.3% gel (Study 1) or trifarotene 0.005% cream (Study 2), and one control patch (no product) placed on their upper back. Skin irritation was assessed and patches were replaced every 2-3 days. RESULTS: In Study 1, tazarotene 0.045% lotion and adapalene 0.3% gel were both mildly irritating, though irritation was lower overall with tazarotene 0.045% lotion. In Study 2, significantly greater irritation was observed with trifarotene 0.005% cream than tazarotene 0.045% lotion, beginning two days after the first patch application and at each subsequent visit. In sub-analyses of data from both studies, irritation among participants with acne was similar to the overall study populations. CONCLUSIONS: In two head-to-head studies comparing the irritation potential of third- and fourth-generation retinoids, tazarotene 0.045% lotion was significantly less irritating than trifarotene 0.005% cream and numerically less irritating than adapalene 0.3% gel.
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Acné Vulgar , Fármacos Dermatológicos , Adulto , Humanos , Adapaleno , Fármacos Dermatológicos/efectos adversos , Naftalenos , Retinoides , Acné Vulgar/tratamiento farmacológico , Emolientes , Método Doble Ciego , Resultado del TratamientoRESUMEN
Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.
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Nanofibras , Psoriasis , Ratas , Animales , Alcohol Polivinílico/química , Nanofibras/química , Povidona/química , Preparaciones de Acción Retardada , Ratas Wistar , Psoriasis/tratamiento farmacológicoAsunto(s)
Fármacos Dermatológicos , Psoriasis , Humanos , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Aminopiridinas/efectos adversos , Benzamidas/efectos adversos , Ciclopropanos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Resultado del Tratamiento , Administración Tópica , Administración Cutánea , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. OBJECTIVE: Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. RESULTS: In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting 'low/not' oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSIONS: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne.