RESUMO
Alopecia areata (AA) is a non-scarring tissue-specific autoimmune disorder. Many therapeutic modalities are available for the treatment of AA, but none has yet proven to be uniformly effective. Fractional carbon dioxide (FRCO2) laser has been introduced as a treatment modality for AA. The objective is to evaluate and compare the efficacy and safety of FRCO2 laser in treatment of AA alone or in combination with betamethasone valerate cream. 30 patients were assigned to one of the following groups, Group A FRCO2, Group B FRCO2 plus betamethasone valerate cream or Group C (betamethasone valerate cream). Patients received eight laser sessions 2 weeks apart, treatment period was 4 months. A statistically significant decrease in SALT score, dystrophic hair and a statistically significant increase in terminal hair was observed in all groups. Patient satisfaction level and reduction in SALT score were significantly higher among FRCO2 and FRCO2 plus betamethasone valerate group. However, no statistical significant difference was found between FRCO2 group and FRCO2 combined with betamethasone valerate cream group. FRCO2 laser is a safe and effective treatment modality for AA when used alone or in combination with betamethasone valerate cream. However, it was found superior to betamethasone valerate cream monotherapy.
Assuntos
Alopecia em Áreas , Lasers de Gás , Humanos , Valerato de Betametasona/uso terapêutico , Alopecia em Áreas/tratamento farmacológico , Dióxido de Carbono/uso terapêutico , Lasers de Gás/efeitos adversos , Resultado do Tratamento , Betametasona/uso terapêuticoRESUMO
INTRODUCTION: This is a randomised, multi-centre, open-label, phase II study to evaluate the efficacy of betamethasone valerate ointment on radiation-induced oral mucositis in patients with head and neck cancer undergoing concomitant radiotherapy with cisplatin or cetuximab. METHODS AND ANALYSIS: The trial will take place at seven hospitals in Japan. Patients will be randomised (1:1) into betamethasone and control groups after the occurrence of grade 1 oral mucositis. In the betamethasone group, patients will use betamethasone valerate ointment five times a day, in addition to usual oral hygiene guidance. The primary endpoint is the incidence and onset time of grade 3 oral mucositis. The secondary endpoints are the incidence and onset time of grade 2 oral mucositis, incidence and onset time of oral candidiasis, completion of radiation therapy and adverse events. Target accrual is 102 patients with a two-sided type I error rate of 5% and 80% power to detect an 80% risk reduction in the incidence of grade 3 oral mucositis. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Review Board of Nagasaki University (No. CRB20-009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publication. The datasets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs071200013.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Lesões por Radiação , Estomatite , Valerato de Betametasona/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estudos Multicêntricos como Assunto , Pomadas/uso terapêutico , Neoplasias Orofaríngeas/radioterapia , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estomatite/tratamento farmacológico , Estomatite/etiologia , Estomatite/prevenção & controleRESUMO
Predicting the dermal bioavailability of topically delivered drugs is challenging. In this work, minimally invasive stratum corneum (SC) sampling was used to quantify the delivery of betamethasone valerate (BMV) into the viable skin. Betnovate® cream (0.1% w/w BMV) was applied at three doses (2, 5, and 10 mg cm-2) to the ventral forearms of 12 healthy volunteers. The mass of drug in the SC was measured using a validated tape-stripping method (a) after a 4-h "uptake" period, and (b) following a 6-h "clearance" period subsequent to cream removal. Concomitantly, the skin blanching responses to the same doses were assessed with a chromameter over 22 h post-application. BMV uptake into the SC was significantly higher for the 5 mg cm-2 dose compared to those of 2 and 10 mg cm-2. In all cases, ~30% of the drug in the SC at the end of the uptake period was cleared in the subsequent 6 h. From the SC sampling data, the average drug flux into the viable epidermis and its first-order elimination rate constant from the SC were estimated as 4 ng cm-2 h-1 and 0.07 h-1, respectively. In contrast, skin blanching results were highly variable and insensitive to the dose of cream applied. The SC sampling method was able to detect a 50% difference between two applied doses with 80% power; detection of a 20% difference would require a larger sample size. SC sampling enabled quantitative metrics describing corticosteroid delivery to the viable epidermis to be determined.
Assuntos
Glucocorticoides , Absorção Cutânea , Valerato de Betametasona , Epiderme , Humanos , Pele/metabolismoRESUMO
Glucocorticoids represent the standard gold treatment of inflammation in asthmatic patients. More recently, H2S has been described to exert positive effect on this disease. Bearing in mind that an improved pharmacological activity and a reduced toxicity can be obtained through hybridization of different molecules, simultaneously modulating multiple targets, we designed and synthesized novel betamethasone 17-valerate and triamcinolone acetonide hybrids with well-known H2S-donor moieties. Synthesized compounds have been evaluated for the potential H2S-releasing profile both in cell-free environment and into the cytosol of bronchial smooth muscle cells (BSMCs). The two hybrids 4b and 5b were investigated by molecular modelling studies and results indicated that the steric accessibility of the isothiocyanate carbon atom can account for their different H2S releasing properties. Furthermore, the most promising derivatives 4b and 5b have been tested for inhibitory effect on mast cell degranulation and for the ability to induce cell membrane hyperpolarization in BSMCs. Significant inhibitory effect on mast cell degranulation was assessed, resulting to reduce ß-hexosaminidase release more efficiently than the corresponding native drugs. Both compounds determined a massive membrane hyperpolarization of BSMCs and proved to be 4-fold more effective compared to reference compound NS1619. These effects represent an enrichment of the pharmacological activity of the native drugs.
Assuntos
Valerato de Betametasona/farmacologia , Brônquios/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Mastócitos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Triancinolona Acetonida/farmacologia , Valerato de Betametasona/química , Brônquios/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Sulfeto de Hidrogênio/química , Mastócitos/metabolismo , Modelos Moleculares , Estrutura Molecular , Miócitos de Músculo Liso/metabolismo , Relação Estrutura-Atividade , Triancinolona Acetonida/químicaRESUMO
PURPOSE: We assessed the role of topical betamethasone as a prophylactic agent in patients receiving radiation for head and neck malignancies. METHODS AND MATERIALS: This randomized, open-label, phase 3 trial was completed at a single research institute. Patients receiving curative radiation for head and neck cancer were randomized into 2 groups of 75 patients each by computer-generated permuted block random assignment. Patients in the test arm applied 0.1% topical betamethasone valerate cream once a day, after radiation. Patients in the control arm received best supportive care. The Radiation Therapy Oncology Group acute toxicity grading scale was used to assess radiation dermatitis after every fifth fraction until completion and at 2 weeks after treatment. Primary outcome in both arms was the proportion of patients who developed grade 2 and 3 acute skin reaction. The trial is registered at the Central Trial Registry of India (CTRI/2017/04/008298). RESULTS: Between April 15, 2017, and October 30, 2018,150 patients were randomized into the study, with 75 patients in each arm. Fourteen patients in the test arm and 15 patients in the control arm did not complete the intended treatment. Per the intention-to-treat analysis, 25 of 75 patients (33.3%) and 38 of 75 patients (50.7%) developed grade 2 or greater radiation dermatitis in the test and control arms, respectively (absolute difference, 17.4%; 95% confidence interval, 4%-30%; P = .032). Fifteen of 75 patients (20%) developed grade 3 reactions in the test arm compared with 18 of 75 patients (24%) in the control arm (absolute difference, 4%; 95% confidence interval, 7%-15%; P = .554). CONCLUSION: Although prophylactic use of betamethasone significantly reduced the composite outcome of the proportion of patients developing grade 2 and grade 3 radiation dermatitis, it did not reduce the proportion of patients developing the clinically significant outcome of grade 3 radiation dermatitis.
Assuntos
Valerato de Betametasona/administração & dosagem , Valerato de Betametasona/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Radiodermite/prevenção & controle , Doença Aguda , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Anti-Infecciosos Locais/efeitos adversos , Valerato de Betametasona/administração & dosagem , Queilite/tratamento farmacológico , Dermatite Alérgica de Contato/tratamento farmacológico , Eczema/tratamento farmacológico , Ácido Fusídico/administração & dosagem , Onicomicose/tratamento farmacológico , Óleo de Melaleuca/efeitos adversos , Administração Tópica , Anti-Infecciosos Locais/uso terapêutico , Valerato de Betametasona/uso terapêutico , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Feminino , Ácido Fusídico/uso terapêutico , Humanos , Pessoa de Meia-Idade , Testes do Emplastro , Extratos Vegetais/efeitos adversos , Óleo de Melaleuca/uso terapêuticoRESUMO
Topical corticosteroid therapies are widely utilized, despite the controversial results of corticoid therapy in irritant contact dermatitis as a local inflammatory reaction after repeated or single skin exposure to a chemical substance. Although corticoids may reduce the inflammatory response to the irritant, their antiproliferative effects may reduce skin barrier recovery while allowing further penetration of irritants if exposure continues. This overview reexamines the efficacy of corticosteroids in irritant contact dermatitis therapy, and with the minimal controlled experimental data currently available, notes the need for same-in this common clinical entity.
Assuntos
Dermatite Irritante/tratamento farmacológico , Glucocorticoides/uso terapêutico , Administração Cutânea , Valerato de Betametasona/uso terapêutico , Clobetasol/uso terapêutico , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/uso terapêutico , Pomadas , Triancinolona Acetonida/uso terapêutico , Perda Insensível de Água/efeitos dos fármacosRESUMO
Staphylococcus aureus is a resident skin bacterium involved in the exacerbation of atopic dermatitis. Here we report that S. aureus regulates the tricarboxylic acid (TCA) cycle via the production of pyruvate for tolerance to betamethasone valerate (BV), an anti-inflammatory drug used in the treatment of atopic dermatitis. The addition of BV or clobetasol propionate to the medium among 5 different anti-inflammatory steroids delayed the growth of S. aureus. Comprehensive gene expression analysis by RNA-seq revealed that BV increased the expression of genes related to glycolysis in S. aureus. Pyruvate, a product of glycolysis, suppressed the S. aureus growth inhibition by BV. The addition of oxaloacetate, a compound in the TCA cycle biosynthesized from pyruvate, was also suppressed the inhibitory effect of BV. Malonate, an inhibitor of succinate dehydrogenase in the TCA cycle, increased the inhibitory effect of BV on the growth of S. aureus. These findings suggest that S. aureus promotes tolerance to BV, an anti-inflammatory steroid, by regulating the TCA cycle via the production of pyruvate.
Assuntos
Valerato de Betametasona/toxicidade , Ciclo do Ácido Cítrico/efeitos dos fármacos , Ácido Pirúvico/farmacologia , Staphylococcus aureus/metabolismo , Malonatos/farmacologia , Ácido Oxaloacético/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Esteroides/farmacologiaRESUMO
STUDY OBJECTIVE: To determine the subtypes of labial adhesion (LA) and arrange treatment options accordingly. DESIGN AND SETTING: Patients who presented to our clinic with LA between July 2016 and February 2018 were divided into 4 groups. Location of the adhesion area, thickness of the adhesive tissue, and response to topical steroid (betamethasone valerate 0.1% ointment) therapy were identified as common features. PARTICIPANTS: Seventy-five prepubertal girls. INTERVENTIONS AND MAIN OUTCOME MEASURES: To determine the subtypes of the LA and evaluate the treatment response of patients in each subtype group. RESULTS: LA was divided into 4 subtypes according to their common characteristics. For patients with type I, 2 weeks of topical steroid treatment resulted in complete recovery (100%). For those with type II, 12 (80%) patients had complete response to topical steroid treatment for an average of 3 weeks. Type III and IV patients were completely unresponsive to topical steroid treatment. CONCLUSION: Classification of LA patients into subtypes and determination of treatment on the basis of this classification make a major contribution in planning the treatment of patients, not by trial-and-error, but using a predetermined strategy.
Assuntos
Anti-Inflamatórios/administração & dosagem , Valerato de Betametasona/administração & dosagem , Aderências Teciduais/tratamento farmacológico , Doenças da Vulva/tratamento farmacológico , Administração Tópica , Adolescente , Protocolos Clínicos , Feminino , Humanos , Estudos Retrospectivos , Aderências Teciduais/classificação , Doenças da Vulva/classificaçãoRESUMO
The present study elucidates the development of an accurate, precise and simple simultaneous estimation method for the routine analysis of Betamethasone Valerate (BV) and Tazarotene (TZ). This combination is widely used in the treatment of psoriasis. No method has been reported so far for the simultaneous estimation of BV and TZ in topical dosage forms. The method proposed by this study for the quantification of BV and TZ is the Absorption factor method. The developed method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline. The validated method was found to be linear in a concentration range of 10-38 µg/mL and 4-14 µg/mL for BV and TZ respectively with a regression coefficient >0.990. The method was validated for accuracy and precision which revealed the recovery of >99.80% with RSD <2.0. The method was found to be precise with RSD <2% for inter and intraday. The developed method was employed for quantification of BV and TZ in lipid based nanocarriers formulation and their in-vitro drug release samples. Further, the developed method was successfully applied for the estimation of BV and TZ in the ex-vivo skin matrix. This showed that the method can sensitively determine the drugs in aqueous and biological samples.
Assuntos
Valerato de Betametasona/análise , Lipídeos/química , Ácidos Nicotínicos/análise , Pele/efeitos dos fármacos , Espectrofotometria Ultravioleta , Administração Tópica , Calibragem , Química Farmacêutica/métodos , Humanos , Técnicas In Vitro , Limite de Detecção , Microscopia de Força Atômica , Nanotecnologia , Análise de Regressão , Reprodutibilidade dos Testes , Solubilidade , Solventes/químicaRESUMO
Introduction: Topical corticosteroids, available in an array of vehicles are used to control a variety of inflammatory skin diseases. Patients preferences for different vehicles may affect their willingness to use treatment. We assess corticosteroid vehicle preference and potential impact of topical characteristics on adherence and quality of life in patients with psoriasis.Methods: Subjects with psoriasis were recruited from Wake Forest University Dermatology Clinic. Subjects sampled desoximetasone 0.25% spray, betamethasone valerate 0.1% cream, triamcinolone acetonide 0.1% ointment, fluocinonide 0.05% gel, betamethasone valerate 0.1% lotion, clobetasol propionate 0.05% foam, and fluocinonide 0.05% solution in a predetermined randomized order. Subjects completed a Vehicle Preference Measure, Determinants of Adherence Measure, and a Determinants of Quality of Life Measure.Results: Patients preferences for the various products were highly variable. Regarding Determinants of Adherence, patients perception of absorption of the medication was ranked as 'quite important/extremely important' by 85% of total subjects. A majority of patients rated medication side effects as 'quite important/extremely important' when asked to consider topical characteristics effect on quality of life.Discussion: There was wide variation in patient preference for topical medication vehicles used for treating psoriasis. Several vehicle characteristics were considered important to adherence. Given the marked variation in vehicle preference, topical treatment should be individualized according to patients preferences.
Assuntos
Glucocorticoides/uso terapêutico , Veículos Farmacêuticos/química , Psoríase/tratamento farmacológico , Administração Tópica , Valerato de Betametasona/efeitos adversos , Valerato de Betametasona/química , Valerato de Betametasona/uso terapêutico , Clobetasol/efeitos adversos , Clobetasol/química , Clobetasol/uso terapêutico , Desoximetasona/efeitos adversos , Desoximetasona/química , Desoximetasona/uso terapêutico , Composição de Medicamentos , Feminino , Fluocinonida/efeitos adversos , Fluocinonida/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/química , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/psicologia , Psoríase/patologia , Qualidade de VidaRESUMO
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.
Assuntos
Valerato de Betametasona/análise , Nanopartículas/química , Ácidos Nicotínicos/análise , Animais , Valerato de Betametasona/metabolismo , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Camundongos , Ácidos Nicotínicos/metabolismo , Pele/química , Pele/metabolismoRESUMO
BACKGROUND: An uncircumcised male infant with a history of urinary tract infection (UTI), physiologic phimosis, and a normal renal ultrasound is a common patient referred to pediatric urology clinics. Topical steroid creams have been shown to effectively release physiologic phimosis. OBJECTIVE: The objective of this study was to test the hypothesis that use of steroid cream for physiologic phimosis is associated with a lower UTI recurrence in uncircumcised male infants with normal renal ultrasounds. STUDY DESIGN: Uncircumcised males younger than 12 months referred for a UTI with a normal renal ultrasound were included. A longitudinal data set was created, and recurrent UTIs were identified. The proportion with a recurrent UTI was compared between those who received a prescription for a steroid cream for phimosis and those who did not. The morbidity of the initial and recurrent UTIs was also described. The association of recurrent UTI with vesicoureteral reflux (VUR) was also evaluated. RESULTS: A total of 192 uncircumcised males with a median age of 5.8 months (interquartile range [IQR]: 3.5-7.9 months) were included. Twenty-seven patients were treated with a course of betamethasone valerate 0.1% cream, and 165 were not (Summary Table). There were no significant differences between groups in the frequency of voiding cystourethrogram (VCUG), diagnosis of VUR, or use of continuous prophylactic antibiotics (CAP). During a median follow-up of 8.7 months (IQR: 3.1-17.5 months), none of the patients treated with steroid cream had a recurrent UTI compared with 27 of 165 (16%) patients not treated (P = 0.02). Among the 173 patients whose initial UTI was febrile, recurrent febrile UTIs occurred in no treated patients and 23 of 150 (15%) untreated patients (P = 0.047). DISCUSSION: The results of this study are consistent with those of a previous randomized trial of steroid cream for physiologic phimosis which found lower recurrent UTI in those whose foreskins became retractable. In addition, the results are consistent with the declining incidence of UTIs in uncircumcised males mirroring the natural history of physiologic phimosis resolving. This study is limited by its retrospective nature and non-standardized follow-up. CONCLUSION: The use of steroid cream for physiologic phimosis is associated with a decreased risk of recurrent UTIs in uncircumcised male infants with a normal renal ultrasound. In this group, steroid cream for physiologic phimosis is a well-tolerated and simple alternative to circumcision to potentially decrease risk of recurrent UTI.
Assuntos
Valerato de Betametasona/administração & dosagem , Rim/diagnóstico por imagem , Fimose/tratamento farmacológico , Ultrassonografia/métodos , Infecções Urinárias/complicações , Administração Tópica , Cistografia , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Incidência , Lactente , Masculino , Pomadas/administração & dosagem , Fimose/complicações , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/epidemiologiaRESUMO
The aim of the present study was to assess the potential of biocompatible polymeric nanosheets as topical and transdermal drug-delivery devices. Nanosheets are two-dimensional nanostructures with a thickness in the nanometer order, and their extremely large aspect ratios result in unique properties, including high transparency, flexibility, and adhesiveness. Nanosheet formulations containing betamethasone valerate (BV) as a model drug and consisting of poly (L-lactic acid) or poly (lactic-co-glycolic) acid were fabricated through a spin-coating-assisted layer-by-layer method using a water-soluble sacrificial membrane. The fabricated formulations could incorporate and release higher amounts of BV compared with a commercial ointment, and the amounts could be controlled by the polymers used, the amount of BV added, and the use of controlled-release membranes. The presence of BV had a minimal effect on thickness, transparency, adhesiveness, and moisture permeability of nanosheets, permitting their application to any area of skin for a long period of time. Therefore, this biocompatible polymeric nanosheet formulation represents a novel and promising topical and transdermal drug delivery device, which has potential to deliver drugs regardless of the area of skin.
Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/administração & dosagem , Poliésteres/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Administração Tópica , Adulto , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Valerato de Betametasona/administração & dosagem , Valerato de Betametasona/química , Liberação Controlada de Fármacos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/química , Humanos , Masculino , Nanoestruturas/química , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Pelados , Pele/metabolismo , Suínos , Adulto JovemRESUMO
OBJECTIVE: To investigate if it was feasible to quantify the renal excretion of topically applied corticosteroids by 19F MRS. MATERIALS AND METHODS: Five participants, one healthy and four with skin diseases, were treated with ointment containing betamethasone 17-valerate. Urine samples were collected for up to 87 h after the initial application. A sample of ointment mixed with urine served as a study control. Organic fractions were obtained after sample freeze drying, and resolved in deuterated chloroform prior to acquisition of 19F MR spectra at 470 MHz for typically 8 h. RESULTS: We detected fluorine signals in 40 of the 62 fractions of organic extracts. The corticosteroid was detected in samples from all patients, ranging from 0.1 to 2.8% of the applied steroid. No fluorine signal was obtained in samples from the healthy volunteer. DISCUSSION: 19F MRS can be utilized to detect topically applied corticosteroids in urine. However, more work is required to optimize and control for extraction procedures, complete spectral assignments and reliable quantification.
Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/urina , Valerato de Betametasona/química , Imagem por Ressonância Magnética de Flúor-19 , Espectroscopia de Ressonância Magnética , Dermatopatias/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Clorofórmio , Dermatite de Contato/tratamento farmacológico , Dermatite de Contato/urina , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Projetos Piloto , Prurido/tratamento farmacológico , Prurido/urina , Psoríase/tratamento farmacológico , Psoríase/urina , Pele/efeitos dos fármacos , Dermatopatias/urina , Urinálise/métodosRESUMO
Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (< 300 ± 28 nm), higher zeta potential (+ 58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that HA-BMV-CS-NPs displayed Fickian diffusion-type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency of BMV was comparatively higher in case of BMV-CS-NPs; however, the amount of drug retained into the epidermis and the dermis was comparatively higher in case of HA-BMV-CS-NPs, compared to BMV-CS-NPs. Conclusively, we anticipate that HA-BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.
Assuntos
Valerato de Betametasona , Quitosana , Sistemas de Liberação de Medicamentos , Glucocorticoides , Ácido Hialurônico , Nanopartículas , Animais , Valerato de Betametasona/administração & dosagem , Valerato de Betametasona/química , Quitosana/administração & dosagem , Quitosana/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Glucocorticoides/administração & dosagem , Glucocorticoides/química , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Cinética , Nanopartículas/administração & dosagem , Nanopartículas/química , Ratos Wistar , Pele/metabolismo , Absorção CutâneaRESUMO
Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.
Assuntos
Anti-Inflamatórios/administração & dosagem , Valerato de Betametasona/administração & dosagem , Administração Tópica , Animais , Anti-Inflamatórios/química , Valerato de Betametasona/química , Quitosana , Dermatite Atópica/tratamento farmacológico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Pressão , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , SolventesRESUMO
BACKGROUND: Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D3 analogs (VD3 As). OBJECTIVE: To compare the effects of a VD3 A maxacalcitol and betamethasone valerate (BV) steroid lotion on topical imiquimod (IMQ)-induced psoriasiform skin inflammation. METHODS: Female BALB/c mice were treated with vehicle, maxacalcitol or BV lotion on the skin for 3 days, and IMQ cream for 6 days. q-PCR, H&E, immunohistochemistry and immunofluorescence studies were performed on skin samples. Additionally, mice were treated with vehicle, maxacalcitol or BV lotion for 3 days and CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25- cells from each group were isolated from lymph nodes. Adoptive transfer of the cells was performed on recipient mice which were treated with IMQ cream for 6 days, and skin samples were obtained for q-PCR and H&E staining. RESULTS: Maxacalcitol and BV were comparable in regards clinical improvement, although maxacalcitol reduced the MHC Class II+ inflammatory cell infiltration more than BV in IMQ skin. While both treatments downregulated IL-17 A, IL-17 F, IL-22, IL-12p40, TNF-α and IL-6 mRNA expression levels, only maxacalcitol downregulated IL-23p19 expression. Significantly increased Foxp3+ cell infiltrations and IL-10 expression were noted in maxacalcitol-treated IMQ skin. Adoptive transfer of Treg cells from maxacalcitol-treated donor mice improved IMQ-induced inflammation clinically and histopathologically more than the recipients of Treg cells from BV-treated donor groups, showing reduced levels of inflammatory cytokines and increased IL-10 expression. CONCLUSION: These results indicate that maxacalcitol reduces psoriasiform skin inflammation by inducing Treg cells as well as downregulating IL-23 and IL-17 production.