Biodegradable calcium carbonate carriers for the topical delivery of clobetasol propionate.

Inflammatory dermatoses represent a global problem with increasing prevalence and recurrence among the world population. Topical glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs in dermatology due to a wide range of their therapeutic actions, which, however, have numerous local and systemic side effects. Hence, there is a growing need to create new delivery systems for GCs, ensuring the drug localization in the pathological site, thus increasing the effectiveness of therapy and lowering the risk of side effects. Here, we propose a novel topical particulate formulation for the GC clobetasol propionate (CP), based on the use of porous calcium carbonate (CaCO3) carriers in the vaterite crystalline form. The designed carriers contain a substantially higher CP amount than conventional dosage forms used in clinics (4.5% w/w vs. 0.05% w/w) and displayed a good biocompatibility and effective cellular uptake when studied in fibroblasts in vitro. Hair follicles represent an important reservoir for the GC accumulation in skin and house the targets for its action. In this study, we demonstrated successful delivery of the CP-loaded carriers (CP-CaCO3) into the hair follicles of rats in vivo using optical coherent tomography (OCT). Importantly, the OCT monitoring revealed the gradual intrafollicular degradation of the carriers within 168 h with the most abundant follicle filling occurring within the first 48 h. Biodegradability makes the proposed system especially promising when searching for new CP formulations with improved safety and release profile. Our findings evidenced the great potential of the CaCO3 carriers in improving the dermal bioavailability of this poorly water-soluble GC.

Development of clobetasol-loaded biodegradable nanoparticles as an endodontic intracanal medicament.

AIM: The aim of current study is the development and optimization of biodegradable polymeric nanoparticles (NPs) to be used in the field of Endodontics as intracanal medication in cases of avulsed teeth with extended extra-oral time, utilizing PLGA polymers loaded with the anti-inflammatory drug clobetasol propionate (CP). METHODOLOGY: CP-loaded nanoparticles (CP-NPs) were prepared using the solvent displacement method. CP release profile from CP-NPs was assessed for 48 h against free CP. Using extracted human teeth, the degree of infiltration inside the dentinal tubules was studied for both CP-NPs and CP. The anti-inflammatory capacity of CP-NPs was evaluated in vitro measuring their response and reaction against inflammatory cells, in particular against macrophages. The enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokine release of IL-1ß and TNF-α. RESULTS: Optimized CP-NPs displayed an average size below 200 nm and a monomodal population. Additionally, spherical morphology and non-aggregation of CP-NPs were confirmed by transmission electron microscopy. Interaction studies showed that CP was encapsulated inside the NPs and no covalent bonds were formed. Moreover, CP-NPs exhibited a prolonged and steady release with only 21% of the encapsulated CP released after 48 h. Using confocal laser scanning microscopy, it was observed that CP-NPs were able to display enhanced penetration into the dentinal tubules. Neither the release of TNF-α nor IL-1ß increased in CP-NPs compared to the LPS control, displaying results similar and even less than the TCP after 48 h. Moreover, IL-1ß release in LPS-stimulated cells, decreased when macrophages were treated with CP-NPs. CONCLUSIONS: In the present work, CP-NPs were prepared, optimized and characterized displaying significant increase in the degree of infiltration inside the dentinal tubules against CP and were able to significantly reduce TNF-α release. Therefore, CP-NPs constitute a promising therapy for the treatment of avulsed teeth with extended extra-oral time.

Novel effect of topical Roquinimex and its combination with Clobetasol on an imiquimod-induced model of psoriasis in mice.

Psoriasis is a chronic inflammatory skin condition affecting multiple systems and the skin, with topical therapy representing the fundamental treatment modality for psoriasis. Investigate the effect of topical Roquinimex (ROQ) alone and combined with Clobetasol propionate (CLO) on imiquimod (IMQ)-induced mouse model as a novel approach to treating psoriasis. Sixty male Swiss Albino mice were divided into six groups of ten mice; all groups except the negative control received IMQ cream 5% (62.5 mg) as a once-daily topical application for six days. On the seventh day, five groups (except negative control) received one of the following treatments for eight days: no treatment (positive control), Petrolatum gel 15% as a twice-daily topical application (Petrolatum control), CLO 0.05% ointment once daily, ROQ ointment 1% w/w twice daily topically, topical preparation of 0.025% CLO ointment combined with ROQ ointment 0.5% w/w twice daily; the total duration of the study is 14 days. The clinical, pathological, and laboratory effects were then measured. The use of ROQ ointment alone or combined with CLO resulted in significant improvement in psoriasis lesions (measured by Baker's and PASI scores) compared to positive control groups (2.15±1.08, 1.60±0.61, 9.00±0.00, and 7.60±0.84, respectively for Baker's score) (1.50±1.08, 1.30±0.95, 11.70±0.48, 9.30±0.67, respectively for PASI score), a similar improvement seen for various inflammatory markers, including interleukin (IL)-10 (140.53±60.68, 285.63±92.16, 31.83±3.03, and 92.50±27.13 pg/ml, respectively), IL-17 (126.58±40.98, 124.26±61.40, 553.04±141.32, and 278.52±100.27 pg/ml, respectively), tumor necrosis factor-α (72.34±23.40, 30.11±7.01, 807.13±500.06, and 281.79±240.17 pg/ml, respectively), and vascular endothelial growth factor (109.71±29.35, 80.96±24.58, 552.20±136.63, 209.56±73.31 pg/ml and respectively). Roquinimex exerts its antipsoriatic effect through multiple mechanisms; its combination treatment with Clobetasol is a promising therapy for managing psoriasis.

Fenómeno infrecuente la co-localización de alopecia frontal fibrosante y vitiligo en un varón: informe de un caso / Infrequent phenomenon the co-localization of fibrosing frontal alopecia and vitiligo in a male: case repor

La alopecia frontal fibrosante es una alopecia cicatricial que se caracteriza por la recesión de la línea de implantación frontotemporal que afecta principalmente a mujeres caucásicas en edad posmenopáusica y rara vez a hombres. Actualmente los mecanismos específicos de desarrollo continúan en estudio; sin embargo hay varias hipótesis sobre la asociación de la alopecia frontal fibrosante con otros trastornos autoinmunitarios. Se comunica el caso de un paciente masculino de 58 años con alopecia frontal fibrosante en áreas comprometidas por vitiligo. (AU)

Frontal fibrosing alopecia is a cicatricial alopecic characterized by progressive regression of the frontotemporal hairline. It usually affects postmenopausal caucasian women, and rarely men. Currently the specific mechanisms of development remain unknown, however there are several hypotheses about the association of frontal fibrosing alopecia with other autoimmune disorders. The case of a 58-year-old male patient with frontal fibrosing alopecia in areas affected by vitiligo. (AU)

Topical steroid containing combinations: Burden of adverse effects and why the recent regulatory action may not be enough.

OBJECTIVES AND METHODS: In September 2018, the government of India banned 328 fixed dose combinations (FDCs), 24 of which are combinations containing topical steroids. To assess what impact can be expected from this regulatory action, we analyzed reports of adverse drug events due to topical corticosteroids at a hospital-based pharmacovigilance center between January 2017 and August 2018. RESULTS: Among 34 different steroid-containing FDCs responsible for 485 reports of ADEs with topical steroids, only three preparations, accounting for 50.10% of ADEs, come under the umbrella of the recent ban. Clobetasone propionate (68.87%) and betamethasone (28.45%) were the corticosteroids most frequently associated with adverse events. Most of the steroid preparations (87.84%) had been bought without a prescription for the treatment of dermatophytoses (76.70%). Males (77.73%) were predominantly affected, and nearly half (47.43%) of the patients were between 21 and 30 years of age. Skin atrophy (50.10%), striae (25.54%), and hypopigmentation (19.79%) were the major ADEs. CONCLUSION: Nearly half of the cutaneous adverse effects were due to topical steroid combinations which are still widely available over the counter.

Acitretin-induced periungual pyogenic granulomas and review.

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.

Clobetasol Compared With Fractionated Carbon Dioxide Laser for Lichen Sclerosus: A Randomized Controlled Trial.

OBJECTIVE: To compare 6-month safety and efficacy outcomes of fractionated CO2 laser (laser) with topical clobetasol propionate (steroid) for treatment of symptomatic vulvar lichen sclerosus. METHODS: We conducted a single-center randomized controlled trial that compared fractionated CO2 laser with steroid treatment for patients with biopsy-proven lichen sclerosus. Randomization was stratified by prior clobetasol propionate use. The primary outcome was mean change in Skindex-29 score at 6 months. A total sample size of 52 participants were recruited to detect a mean difference of 16 points on the Skindex-29 (SD±22) with 80% power, based on a one-sided two-sample t test with α=0.05, accounting for 10% attrition. Secondary outcomes included validated subjective and objective measures. Intention-to-treat, per protocol, and regression analysis based on prior steroid exposure were performed. RESULTS: From October 2015 to July 2018, 202 women were screened, 52 were randomized, and 51 completed a 6-month follow-up. No significant difference was found in baseline demographics, symptoms, and physician assessment scores. There was greater improvement in the Skindex-29 score in the laser arm at 6-months (10.9 point effect size, 95% CI 3.42-18.41; P=.007). Overall, 89% (23/27) of patients in the laser group rated symptoms as being "better or much better" compared with 62% (13/24) of patients in the steroid group, P=.07. More patients (81%, 21/27) were "satisfied or very satisfied" with laser treatment compared with steroid treatment (41%, 9/24); P=.01. After stratification for previous steroid use, the significant change of Skindex-29 score was only seen in the previously exposed group. There was one adverse event in each group: minor burning and blistering at the laser site and reactivation of genital herpes 1 week after starting steroid. CONCLUSION: Fractionated CO2 laser treatment showed significant improvement in subjective symptoms and objective measures compared with clobetasol propionate, without serious safety or adverse events at 6 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02573883.

Once-Daily Halobetasol Propionate 0.01% Lotion for Moderate-to-Severe Plaque Psoriasis: Phase 3 Analysis of Hispanic Participants.

BACKGROUND: Psoriasis is a chronic, inflammatory disease that may differ in prevalence and clinical presentation among patients from various racial and ethnic groups. Two phase 3 studies demonstrated efficacy and safety of halobetasol propionate (HP) 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis (NCT02514577, NCT02515097). These post hoc analyses evaluated HP 0.01% lotion in Hispanic participants. METHODS: Participants were randomized (2:1) to receive once-daily HP or vehicle lotion for 8 weeks, with a 4-week posttreatment follow-up. Post hoc efficacy assessments in Hispanic participants (HP, n=76; vehicle, n=43) included treatment success (≥2­grade improvement in Investigator’s Global Assessment and score of ‘clear’ or ‘almost clear’), psoriasis signs, and affected body surface area (BSA). Treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: At week 8, 38.8% of participants achieved treatment success with HP versus 10.3% on vehicle (P=0.001). HP­treated participants achieved greater improvements in psoriasis signs, compared with vehicle (P<0.01 all). HP group had a greater reduction in affected BSA versus vehicle (P=0.001). Treatment-related TEAEs with HP were application site infection and dermatitis (n=1 each). CONCLUSIONS: Once-daily HP 0.01% lotion was associated with significant reductions in disease severity in Hispanic participants with moderate-to-severe psoriasis, with good tolerability and safety over 8 weeks. J Drugs Dermatol. 2021;20(3):252-258. doi:10.36849/JDD.5698.

Topical 0.05% clobetasol cream in the treatment of chronic hand eczema: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic hand eczema (CHE) is a recurrent, frequently disabling skin condition that requires daily skin care to prevent transepidermal water loss, posing a significant burden of society and economy. In recent years, topical 0.05% clobetasol cream is widely used for the treatment of CHE for its efficacy, tolerability and safety. Whereas, no systematic review and meta-analysis has been updated up to now. Therefore, this work aims to assess the effectiveness and safety of topical 0.05% clobetasol cream in patients with CHE. METHODS: Study on topical 0.05% clobetasol cream for CHE will be searched from their inception to December, 2020 with the language restrictions of English and Chinese in 8 databases (PubMed, Cochrane Library, Embase, the web of science, VIP, CNKI, CBM, and WAN FANG). According to the heterogeneity test, a fixed or random-effect model will be used to synthesize data. The primary outcome is the proportion of patients achieving more than 75% reduction in signs and symptoms according to the Hand Eczema Severity Index (HECSI). The secondary outcomes include: scored for 4 different characteristics of the lesions (redness, scaling, lichenification, and pruritus), QoL questionnaire, adverse events, and recurrence events. STATA 13.0 and Review Manager software 5.3 will be used for analysis and synthesis. Two or more reviewers will independently conduct the selection of studies, data extraction, and data analysis. RESULTS: The results of the study expect to provide a high-quality, evidence-based recommendation on topical 0.05% clobetasol cream in the treatment of CHE for clinicians. CONCLUSION: The study will provide scientific and useful evidence for better use of topical 0.05% clobetasol cream in treating CHE. ETHICS AND DISSEMINATION: This study is a protocol for an overview of SRs/MAs that did not involve individual data. Thus, ethical approval is not required. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/SPHVZ.

Clobetasol propionate 0.05% under occlusion for alopecia areata: Clinical effect and influence on intraocular pressure.

Topical corticosteroids are known to be effective in the treatment of alopecia areata, but the potential effects on intraocular pressure are a concern. The purpose of this retrospective study is to evaluate the effect of clobetasol propionate 0.05% under occlusion on patients with active phase alopecia areata and to examine the effects on intraocular pressure. We also wished to see if reducing the frequency of application of clobetasol increased the safety with respect to intraocular pressure. Elevation of intraocular pressure due to topical corticosteroids is unlikely to occur at the dose of 9.8 g or less per week used in this study; however, ophthalmologic examination at the start of treatment was thought to be worthwhile in identifying patients with latent glaucoma.

Optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology.

BACKGROUND: Successful clinical data on halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis are published. This article charts its formulation development. METHODS: Dermal deposition, clinical efficacy, and synergistic effect of HP and TAZ delivered by polymeric emulsion technology was compared to HP 0.05% cream (Ultravate) and TAZ 0.1% cream (Tazorac); skin hydration and barrier maintenance with vehicle lotion through Trans Epidermal Water Loss (TEWL) and corneometry using human cadaver tissue; and steroid potency by vasoconstrictor assay (VCA) in healthy volunteers. Safety and tolerability evaluated in clinical studies and patient preference questionnaire. RESULTS: HP/TAZ lotion, using polymeric emulsion technology demonstrated better active ingredient delivery than HP 0.05% or TAZ 0.1% creams; supported by synergistic clinical data, with high HP potency outcome. Efficacy was rapid and sustained posttreatment. Layering TAZ 0.1% cream onto HP 0.05% cream had a negative effect on receptor phase levels. HP/TAZ lotion provided rapid and sustained increases in skin moisturization and gradually decreases in TEWL. Most subjects responded favorably to questions on the physical attributes of the vehicle lotion. CONCLUSIONS: Fixed combination HP 0.01%/TAZ 0.045% lotion formulation utilizing innovative polymeric emulsion technology and optimal selection of solvents/emollients/humectants, has recently been developed. Features inherent in technology translate into rapid, sustained efficacy, low irritation, and good patient acceptance.