[Simultaneous determination of 83 glucocorticoids in cosmetics by ultra performance liquid chromatography-tandem mass spectrometry].

Glucocorticoids, which are a class of steroidal hormones secreted by the adrenal cortex, have significant anti-inflammatory, immunosuppressive, and anti-allergic effects. Thus, these compounds are widely used in clinical practice. However, the long-term use of cosmetics containing glucocorticoids can lead to serious consequences, such as hormone-dependent dermatitis, hypertension, and other serious injuries. The Safety and Technical Specification for Cosmetics (2015 edition) and Regulation (EC) No. 1223/2009 of the European Parliament and Council on cosmetic products list glucocorticoids as prohibited raw materials. According to the National Medical Products Administration, reports on the illegal addition of glucocorticoids to cosmetics by manufacturers have increased in recent years. Therefore, establishing high-throughput screening methods to ensure the quality and safety of cosmetics is imperative. In this study, a comprehensive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the rapid screening of 83 glucocorticoids in cosmetics. A series of conditions were optimized using three matrices that are commonly used in cosmetics: water, lotion, and cream (o/w-type). Four mobile-phase systems and three chromatographic columns were then optimized to achieve the best separation effects. Various MS parameters, such as the capillary voltages, cone voltages, desolvation gas flow rates, and collision energies of the ion pairs of the target compounds, were also optimized. Furthermore, pretreatment was essential for glucocorticoid determination owing to the complex matrix effects of cosmetics. The analytes were divided into two groups, with lg Kow=4 as the limit, to compare the effects of the extraction solvent on recoveries. The extraction recoveries of target analytes with six extraction methods, namely, extraction with acetonitrile, extraction with acetone, extraction with ethyl acetate, dispersion in saturated sodium chloride solution followed by extraction with acetonitrile, dispersion in saturated sodium chloride solution followed by extraction with acetone, and dispersion in saturated sodium chloride solution followed by extraction with ethyl acetate, were compared. The recoveries from QuEChERS and solid-phase extraction (SPE) purification were also compared. Based on the experimental results, the final sample pretreatment method included acetonitrile vortex dispersion, ultrasonic extraction, and sample loading after filtration. The 83 target compounds were separated on a Thermo Accucore PFP column (100 mm×2.1 mm, 2.6 µm) with 0.1% (v/v) acetic acid in acetonitrile and 0.1% (v/v) acetic acid in water as the mobile phases. The analytes were determined by dynamic multiple-reaction monitoring (MRM) in electrospray positive ionization mode (ESI+) and quantified using the external standard method. Matrix standard curves were used to reduce matrix effects. The calibration curves of the 83 target compounds were linear in the mass concentration range of 2-200 µg/L (r>0.995). At three levels of addition, the recoveries were 74.5%-112.4%, and the relative standard deviations (RSDs, n=6) were 0.8%-9.9%. The limits of detection (LODs, S/N≥3) were 0.001-0.023 µg/g, and the limits of quantification (LOQs, S/N≥10) were 0.002-0.076 µg/g. The developed method was used to detect glucocorticoids in 41 cosmetic samples. Fluocinolone acetonide, beclomethasone dipropionate, desonide 21-acetate, and desonide were detected in four samples. The content range of glucocorticoids in the positive samples was 0.53-634.27 µg/g. Notably, desonide 21-acetate, which is not included in the scope of the statutory detection method, was detected in two batches of samples. In conclusion, the proposed method is simple, sensitive, reliable, and suitable for the high-throughput analysis of the 83 glucocorticoids in cosmetics with different matrices. This method could provide reliable technical support for the daily supervision of cosmetics and serve as a supplement to current glucocorticoid standards.

Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery: Pharmacodynamic and Safety Evaluation.

BACKGROUND: When administered transdermally, desonide is ineffective due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel. METHODS: Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate ® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure safety, atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay. RESULTS: Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of the ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase. CONCLUSION: Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides a higher transdermal potential than other delivery systems. In this study, it was found that nanoemulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has a significant curative effect on dermatitis/eczema in a mouse model and is expected to provide a new, efficient, and low toxic preparation for clinical treatment of dermatitis/eczema through the percutaneous system.

Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation.

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide (p < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm2) in comparison to the commercial gel cream (0.16 µg.cm2). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations (p < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders.

Suppression of toxicity of the mutant huntingtin protein by its interacting compound, desonide.

Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders such as Huntington's disease (HD), which is mainly caused by the mutant huntingtin protein (mHTT), an "undruggable" pathogenic protein with unknown functions. We hypothesized that some of the chemical binders of mHTT may change its conformation and/or stability to suppress its downstream toxicity, functioning similarly to an "inhibitor" under a broader definition. We identified 21 potential mHTT selective binders through a small-molecule microarray­based screening. We further tested these compounds using secondary phenotypic screens for their effects on mHTT-induced toxicity and revealed four potential mHTT-binding compounds that may rescue HD-relevant phenotypes. Among them, a Food and Drug Administration­approved drug, desonide, was capable of suppressing mHTT toxicity in HD cellular and animal models by destabilizing mHTT through enhancing its polyubiquitination at the K6 site. Our study reveals the therapeutic potential of desonide for HD treatment and provides the proof of principle for a drug discovery pipeline: target-binder screens followed by phenotypic validation and mechanistic studies.

Nanoemulgel for Improved Topical Delivery of Desonide: Formulation Design and Characterization.

This research aimed to develop a novel drug delivery system to improve treatment of skin disorders. The system is comprised of a Carbopol 980-based nanoemulgel (NE-gel) containing a desonide (DES; 0.05%, w/w) nanoemulsion (NE), which has a small particle size, high encapsulation efficiency, good thermodynamic stability, good permeation ability, and high skin retention. DES-loaded NE (DES-NE) was prepared by high-pressure homogenization. The developed formulation was characterized by differential scanning calorimetry (DSC), X-ray diffraction, drug release, skin permeation, and drug retention. DES in vitro release and skin permeation studies with different formulations of artificial membrane and rat abdominal skin were performed with the Franz diffusion cell system. Confocal laser scanning microscopy (CLSM) was used to detect the localization and permeation pathways of drugs in the skin. Compared with commercially available gel (CA-gel) and NE, the NE-gel release process conformed to the Higuchi release model (R2 = 0.9813). NE-gel prolonged the drug release time and allowed for reduced administration dose and frequency. The unit cumulative permeation of NE and NE-gel through the skin for 12 h was 63.13 ± 2.78 and 42.53 ± 2.06 µg/cm2, respectively, values significantly higher (p < 0.01) than that of the CA-gel (30.65 ± 1.25 µg/cm2) and CA-cream (15.21 ± 0.97 µg/cm2). The DES-NE and DES NE-gel skin drug retention was significantly higher than commercially available formulations (p < 0.01). Hence, the prepared NE-gel is a potential vehicle for improved topical DES delivery for better treatment of skin disorders.

Clinical efficacy of mucopolysaccharide polysulfate ointment combined with desonide ointment in treatment of infantile eczema.

To observe and analyze the clinical efficacy of mucopolysaccharide polysulfate (MPS) ointment combined with desonide ointment in treatment of infantile eczema. A total of 180 infants who had been treated for eczema at our hospital were enrolled. The patients were divided into control group accepting desonide ointment only and research group accepting mucopolysaccharide polysulfate ointment and desonide ointment. The therapeutic efficacies of two groups were compared. Results: By comparing the total therapeutic efficacy, results showed that the total efficacy of the research group was 96.67%, while that value of the control group was 82.22%, making the total efficacy of the research group significantly higher (p<0.05). And the improvement of the Eczema Area and Severity Index (EASI) score in the research group after drug administration was significantly better than that of the control group (p<0.05). Moreover, there was a greater decrease in the recurrence rate of the research group than that of the control group (p<0.05). Combined application of mucopolysaccharide polysulfate ointment and desonide ointment can achieve better therapeutic effect in treatment of infantile eczema.

The Itch that freckles? Development of lentigines in areas of resolved chronic atopic dermatitis.

We report two pediatric patients with a history of chronic lichenified atopic dermatitis (AD) who subsequently developed eruptive lentigines at sites of resolved AD. The occurrence of this phenomenon in eczematous dermatoses in the absence of topical calcineurin inhibitor (TCI) use is rarely reported in the literature.

Desonide nanoencapsulation with açai oil as oil core: Physicochemical characterization, photostability study and in vitro phototoxicity evaluation.

This study aimed to develop Eudragit® RL 100 nanocapsules loaded with desonide (DES) using açai oil (AO) or medium chain triglycerides (MCT) as oil core. Pre-formulation study showed that AO and MCT are suitable for nanocapsules preparation. The nanocapsules prepared with AO and MCT presented mean particle size around 165 and 131 nm, respectively; polydispersity index values <0.20, positive zeta potential values, drug content close to the theoretical value (0.25 mg mL-1), and DES encapsulation efficiency around 81%, regardless of the oil core (AO or MCT). Considering the photoinstability reported to DES, photodegradation studies were performed. The UV-A (365 nm) and UV-C (254 nm) photodegradation studies revealed less DES degradation when associated to the nanocapsules containing AO in comparison to those with MCT. The in vitro release study showed a biphasic release profile for both nanocapsule suspensions: an initial burst effect followed by a prolonged DES release. In addition, the formulations were considered non-phototoxic at 0.5 mg mL-1 when tested on 3 T3 murine fibroblasts and HaCaT human keratinocytes using the MTT and NRU viability assays. The irritant potential of the prepared nanocapsules and DES in free form were evaluated by HET-CAM method. All formulations were classified as slightly irritant, including the non-associate DES. In conclusion, the nanocapsule formulations developed in this study may be promising for therapeutic applications.

Comparison of Topical, Systemic, and Combined Therapy with Steroids on Idiopathic Granulomatous Mastitis: A Prospective Randomized Study.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a benign disorder of the breast, for which the optimal treatment modality remains missing. METHODS: A total of 124 patients with a histopathologically proven diagnosis of IGM were enrolled in a prospective, randomized parallel arm study. Patients were treated with topical steroids in Group T (n: 42), systemic steroids (0.8 mg/kg/day peroral) in Group S (n: 42), and combined steroids (0.4 mg/kg/day peroral + topical) in Group C (n: 40). Compliance with the therapy, response to the therapy, the duration of therapy, side effects and the recurrence rates were compared. RESULTS: Sixteen patients did not comply with the treatment, and the highest ratio of compliance with therapy was seen in Group T (p < 0.05). Complete clinical regression (CCR) was observed in 90 (83.3%) patients. Response to the treatment (RT) was evaluated radiologically and observed in 89.8% of the patients. There was no statistically significant difference between groups regarding CCR, RT and the recurrence rate. The longest duration of therapy was observed in Group T (22 ± 9.1-week), whereas the shortest was observed in Group S (11.7 ± 5.5-week) (p < 0.001). The systemic side effects were significantly lower in Group T in comparison with Groups S and C (2.4% vs. 38.2% and 30.3%, respectively) (p < 0.001). CONCLUSIONS: The efficiency of the treatment was similar for all groups, both clinically and radiologically. Although the duration of therapy was longer in Group T, the lack of systemic side effects increased the compliance of the patients with the therapy. Therefore, topical steroids would be among first-line treatment options of IGM.

Crusted scabies mimicking an acrodermatitis continua of Hallopeau.

Background: Crusted scabies (CS) is an uncommon, highly contagious, variant of classic scabies. Elevated concentrations of the mite Sarcoptes scabiei var. hominis are found in the skin lesions, which lead to a more exaggerated clinical picture than in classic scabies. This disease is mainly observed in patients with any kind of immunosuppression and relates to Down syndrome. Case report: A pediatric female patient with Down syndrome, who presented a crusty white plaque associated with nail dystrophy and subungual hyperkeratosis affecting the distal portion of the fingers is described. Because of these findings, the diagnosis of acrodermatitis continua of Hallopeau was considered. A punch biopsy was performed, attaining the diagnosis of CS. She received systemic treatment with oral ivermectin, topical treatment with emollient cream and desonide 0.1%. Notorious clinical improvement was observed two weeks after finalizing treatment. Conclusions: CS is variant of scabies prevalent in immunocompromised patients and Down syndrome that can be easily confused with inflammatory pathologies with abnormal epidermal keratinization. This case is considered as an atypical presentation of the disease because of local affection of the fingers and nail dystrophy. The histopathological study was necessary to obtain the diagnosis and rule out differential diagnosis.

Introducción: La escabiasis costrosa (EC) es una variante poco común de sarcoptiosis clásica, altamente contagiosa. Las lesiones poseen una elevada concentración del ácaro Sarcoptes scabiei var hominis, lo que conlleva a un cuadro clínico más extenso que en la escabiasis clásica. Se observa principalmente en pacientes con algún tipo de inmunocompromiso y se relaciona con el síndrome de Down. Caso clínico: Se describe una paciente pediátrica con síndrome de Down quien presentó placas escamosas que afectaron la porción distal de los dedos, asociadas con distrofia ungueal e hiperqueratosis subungueal, por lo que se consideró acrodermatitis continua de Hallopeau como diagnóstico diferencial. Se realizó una biopsia tipo punch con lo que se llegó al diagnóstico de EC. La paciente recibió tratamiento sistémico con ivermectina vía oral y tratamiento tópico con crema hidratante y desonida al 0.1%. Mostró mejoría clínica notoria dos semanas después de finalizar el tratamiento. Conclusiones: La EC es una variante prevalente en pacientes inmunocomprometidos y con síndrome de Down que fácilmente puede confundirse con patologías inflamatorias con alteración de la queratinización epidérmica. Este caso se considera una presentación atípica debido a la afección localizada en los dedos de las manos asociada con distrofia ungueal. El estudio histopatológico fue necesario para realizar el diagnóstico y descartar diagnósticos diferenciales.

Topical Treatment for the Management of Atopic Dermatitis

Atopic dermatitis affects up to 20% of children and continues to increase in prevalence. Effective disease control is aimed at decreasing symptoms and reducing the frequency of flares, which may be complicated by secondary bacterial infections. Although recent advances have produced a number of non-systemic treatment options, topical corticosteroids remain a fundamental component of treatment algorithms. J Drugs Dermatol. 2019;18(2 Suppl):s112-116.

Development of a novel HPLC method for the determination of the impurities in desonide cream and characterization of its impurities by 2D LC-IT-TOF MS.

A novel HPLC method for the determination of the impurities in desonide cream was established and validated for the further improvement of the official monograph in USP. Desonide was well resolved from the photodegradation impurity, which overlapped with desonide in USP method. The method was validated in accordance to the regulatory guidelines recommended by the International Conference on Harmonisation and this validation included specificity, limit of detection, limit of quantification, linearity and accuracy. Four degradation impurities in desonide cream were characterized by a trap-free two-dimensional liquid chromatography coupled to high resolution ion trap/time-of-flight mass spectrometry (2D LC-IT-TOF MS) in positive mode of electrospray ionization. Through the multiple heart-cutting 2D LC approach and online demineralization technique, the problem of incompatibility between non-volatile salt mobile phase and mass spectrometry was solved completely, and the TIC chromatogram of LC-MS could be in conformity with the LC chromatogram of the official analytical method in the peak sequence of impurities. In the first dimension, the column was Phenomenex Kinetex C8 (4.6 mm × 150 mm, 2.6 µm) with a non-volatile salt mobile phase. In the second dimension, the column was Shimadzu Shim-pack GISS C18 (50 mm × 2.1 mm, 1.9 µm) with a volatile salt mobile phase. The structures of four degradation impurities in desonide cream were deduced based on the HPLC-MSn data. The established method in this study was simple and reliable for routine quality control of desonide cream.

The triad of pruritus, xanthomas, and cholestasis: Two cases and a brief review of the literature.

When encountered in children, xanthomas are most commonly associated with a group of disorders known as familial hyperlipidemias. Aside from cosmetic concerns, these xanthomas are typically asymptomatic, but when generalized pruritus is a prominent associated symptom, clinicians should consider a different set of diagnoses that includes cholestasis of the liver. In this article we present two illustrative cases of children with cholestatic disease, pruritus, and xanthomas and discuss other disorders that may include this triad.

Rash on eyebrows and periumbilical region.

Patch testing data indicate that the 5 most prevalent contact allergens out of more than 3700 that are known are: nickel (14.3% of patients tested), fragrance mix (14%), the topical antibiotic neomycin (11.6%), balsam of Peru (used in some perfumes, toiletries, and pharmaceutical items) (10.4%), and the mercury-based vaccine preservative thimerosal (10.4%).

Topical Treatment of Facial Seborrheic Dermatitis: A Systematic Review.

BACKGROUND: Facial seborrheic dermatitis (SD), a chronic inflammatory skin condition, can impact quality of life, and relapses can be frequent. Three broad categories of agents are used to treat SD: antifungal agents, keratolytics, and corticosteroids. Topical therapies are the first line of defense in treating this condition. OBJECTIVE: Our objective was to critically review the published literature on topical treatments for facial SD. METHODS: We searched PubMed, Scopus, Clinicaltrials.gov, MEDLINE, Embase, and Cochrane library databases for original clinical studies evaluating topical treatments for SD. We then conducted both a critical analysis of the selected studies by grading the evidence and a qualitative comparison of results among and within studies. RESULTS: A total of 32 studies were eligible for inclusion, encompassing 18 topical treatments for facial SD. Pimecrolimus, the focus of seven of the 32 eligible studies, was the most commonly studied topical treatment. CONCLUSION: Promiseb®, desonide, mometasone furoate, and pimecrolimus were found to be effective topical treatments for facial SD, as they had the lowest recurrence rate, highest clearance rate, and the lowest severity scores (e.g., erythema, scaling, and pruritus), respectively. Ciclopirox olamine, ketoconazole, lithium (gluconate and succinate), and tacrolimus are also strongly recommended (level A recommendations) topical treatments for facial SD, as they are consistently effective across high-quality trials (randomized controlled trials).

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3.

CONTEXT: Our group previously reported the photoinstability of some desonide topical commercial formulations under direct exposure to UVA radiation. OBJECTIVE: This study aimed to prepare and characterize a gel-cream containing desonide, with greater photostability than the commercial gel-cream (C-GC). Benzophenone-3 (BP-3) was used as a photostabilizing agent. METHODS: The gel-cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized regarding its pH, drug content, spreadability, viscosity, in vitro drug release and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase assay. RESULTS AND DISCUSSION: D-GC presented characteristics compatible with topical application, appropriate drug content and good spreadability, and non-Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability profile, presenting a desonide content of 95.70% after 48 h of exposure to UVA radiation, and stability under room conditions during 60 days. The amount of desonide released from D-GC and C-GC was 57.8 and 51.7 µg/cm2, respectively, measured using the vertical Franz cell. The in vitro skin permeation showed that desonide reached the site of action of the topical corticosteroids, from both formulations; however, the desonide amount retained in the dermis was lower with D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that D-GC presented the same biological effect as C-GC. CONCLUSION: D-GC represents a promising approach to treat dermatological disorders, since it presented satisfactory physicochemical characteristics, the same biological activity as C-GC and superior photostability, conferred by the addition of BP-3 at 0.1%.

Functional interpretation of metabolomics data as a new method for predicting long-term side effects: treatment of atopic dermatitis in infants.

Topical steroids are used for the treatment of primary atopic dermatitis (AD); however, their associated risk of serious complications is great due to the presence of vulnerable lesions in young children with AD. Topical calcineurin inhibitors (TCIs) are steroid-free, anti-inflammatory agents used for topical AD therapy. However, their use is prohibited in infants <2 years of age because of their carcinogenic potential. We conducted a randomized, double-blind trial to evaluate the efficacy of TCIs as a secondary AD treatment for children <2 years of age by comparing 1% pimecrolimus cream with 0.05% desonide cream. We performed urinary metabolomics to predict long-term side effects. The 1% pimecrolimus cream displayed similar efficacy and exceptional safety compared with the 0.05% desonide cream. Metabolomics-based long-term toxicity tests effectively predicted long-term side effects using short-term clinical models. This applicable method for the functional interpretation of metabolomics data sets the foundation for future studies involving the prediction of the toxicity and systemic reactions caused by long-term medication administration.