RESUMO
PURPOSE: Adapalene (AD) is one of the main retinoids used in the topical therapy of acne, an extremely common skin disease usually associated with psychological morbidity. However, like other retinoids, AD is frequently associated with skin irritation. To overcome the skin irritation, we proposed the encapsulation of AD in solid lipid nanoparticles (SLNs) using the ion pair strategy. METHODS: The developed SLN-AD was characterized by high-performance liquid chromatography, differential scanning calorimetry, X-ray diffraction, synchrotron small-angle X-ray scattering, and transmission electron microscopy. In vitro permeation tests using porcine skin and in vivo mice skin irritation test were performed to evaluate, respectively, the drug's skin distribution and the skin irritation. RESULTS: The characterization studies were able to demonstrate that the proposed strategy effectively provided high AD encapsulation in SLNs and its incorporation into a hydrophilic gel. Sustained release, epidermal targeting, and less skin irritation were observed for SLN-AD gel in comparison to the marketed AD gel. CONCLUSIONS: The studies demonstrated that the encapsulation of AD in SLNs through the formation of an ion pair is a valuable alternative to diminish the adverse skin reactions caused by AD and can optimize patient adherence to treatment.
Assuntos
Acne Vulgar/tratamento farmacológico , Adapaleno/farmacologia , Preparações de Ação Retardada/química , Fármacos Dermatológicos/farmacologia , Ácidos Graxos/química , Nanocápsulas/química , Aminas/metabolismo , Animais , Transporte Biológico , Fármacos Dermatológicos/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Epiderme/efeitos dos fármacos , Glicerol/química , Humanos , Íons/química , Transição de Fase , Pele , Absorção Cutânea , Suínos , Temperatura de TransiçãoRESUMO
Abstract Background: Higher skin pH in atopic dermatitis contributes to impaired epidermal barrier. A moisturizer compatible with physiological pH could improve atopic dermatitis. Objective: To determine the effect of a physiologically compatible pH moisturizer in atopic dermatitis. Methods: A randomized half body, double blind, controlled trial involving patients with stable atopic dermatitis was performed. pH-modified moisturizer and standard moisturizer were applied to half body for 6 weeks. Results: A total of 6 (16.7%) males and 30 (83.3%) females participated. Skin pH reductions from week 0, week 2 and 6 were significant at the forearms (5.315 [0.98] to 4.85 [0.54] to 5.04 [0.78], p = 0.02) and abdomen (5.25 [1.01], 4.82 [0.64], 5.01 [0.59], p = 0.00) but not at the shins (5.01 [0.80], 4.76 [0.49], 4.85 [0.79], p = 0.09) with pH-modified moisturizer. Transepidermal water loss (TEWL) at the forearms decreased (4.60 [2.55] to 3.70 [3.10] to 3.00 [3.55], p = 0.00), abdomen (3.90 [2.90] to 2.40 [3.45] to 2.70 [2.25], p = 0.046). SCORAD improved from 14.1 ± 12.75 to 10.5 ± 13.25 to 7 ± 12.25, p = 0.00. In standard moisturizer group, pH reductions were significant at the forearms (5.29 [0.94] to 4.84 [0.55] to 5.02 [0.70], p = 0.00) and abdomen (5.25 [1.09], 4.91 [0.63], 5.12 [0.66], p = 0.00). TEWL at the forearm were (4.80 [2.95], 4.10 [2.15], 4.60 [3.40], p = 0.67), shins (3.80 [1.40], 3.50 [2.35], 4.00 [2.50], p = 0.91) and abdomen (3.70 [2.45], 4.10 [3.60], 3.40 [2.95], p = 0.80). SCORAD improved from 14.2 ± 9.1 to 10.9 ± 10.65 to 10.5 ± 11, p = 0.00. Reduction in pH was observed with both moisturizers while TEWL significantly improved with pH-modified moisturizer. pH-modified moisturizer resulted in greater pH, TEWL and SCORAD improvements however the differences were not significant from standard moisturizer. Study limitation: Skin hydration was not evaluated. Conclusion: Moisturization is beneficial for atopic dermatitis; use of physiologically compatible pH moisturizer is promising.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/química , Creme para a Pele/uso terapêutico , Creme para a Pele/química , Valores de Referência , Fatores de Tempo , Índice de Gravidade de Doença , Método Duplo-Cego , Resultado do Tratamento , Estatísticas não Paramétricas , Epiderme/efeitos dos fármacos , Epiderme/química , Concentração de Íons de Hidrogênio , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Higher skin pH in atopic dermatitis contributes to impaired epidermal barrier. A moisturizer compatible with physiological pH could improve atopic dermatitis. OBJECTIVE: To determine the effect of a physiologically compatible pH moisturizer in atopic dermatitis. METHODS: A randomized half body, double blind, controlled trial involving patients with stable atopic dermatitis was performed. pH-modified moisturizer and standard moisturizer were applied to half body for 6 weeks. RESULTS: A total of 6 (16.7%) males and 30 (83.3%) females participated. Skin pH reductions from week 0, week 2 and 6 were significant at the forearms (5.315 [0.98] to 4.85 [0.54] to 5.04 [0.78], p=0.02) and abdomen (5.25 [1.01], 4.82 [0.64], 5.01 [0.59], p=0.00) but not at the shins (5.01 [0.80], 4.76 [0.49], 4.85 [0.79], p=0.09) with pH-modified moisturizer. Transepidermal water loss (TEWL) at the forearms decreased (4.60 [2.55] to 3.70 [3.10] to 3.00 [3.55], p=0.00), abdomen (3.90 [2.90] to 2.40 [3.45] to 2.70 [2.25], p=0.046). SCORAD improved from 14.1±12.75 to 10.5±13.25 to 7±12.25, p=0.00. In standard moisturizer group, pH reductions were significant at the forearms (5.29 [0.94] to 4.84 [0.55] to 5.02 [0.70], p=0.00) and abdomen (5.25 [1.09], 4.91 [0.63], 5.12 [0.66], p=0.00). TEWL at the forearm were (4.80 [2.95], 4.10 [2.15], 4.60 [3.40], p=0.67), shins (3.80 [1.40], 3.50 [2.35], 4.00 [2.50], p=0.91) and abdomen (3.70 [2.45], 4.10 [3.60], 3.40 [2.95], p=0.80). SCORAD improved from 14.2±9.1 to 10.9±10.65 to 10.5±11, p=0.00. Reduction in pH was observed with both moisturizers while TEWL significantly improved with pH-modified moisturizer. pH-modified moisturizer resulted in greater pH, TEWL and SCORAD improvements however the differences were not significant from standard moisturizer. STUDY LIMITATION: Skin hydration was not evaluated. CONCLUSION: Moisturization is beneficial for atopic dermatitis; use of physiologically compatible pH moisturizer is promising.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/química , Fármacos Dermatológicos/uso terapêutico , Creme para a Pele/química , Creme para a Pele/uso terapêutico , Adolescente , Adulto , Criança , Método Duplo-Cego , Epiderme/química , Epiderme/efeitos dos fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
A simple, stability-indicating, chromatographic method of quantifying spironolactone (SPI) and its metabolite, canrenone (CAN), in the presence of excipients typical in dermatological formulations and skin matrices in studies of passive and iontophoretic permeation was proposed and validated here. SPI and CAN were separated using a reversed-phase column with a mobile phase of methanol-water (60:40, v/v) at a flow rate of 1.0 mL/min. Data were collected with a UV detector at 238 and 280 nm, with retention times of 6.2 and 7.9 min for SPI and CAN, respectively. The method was precise, accurate and linear (r2 > 0.99) in a concentration range of 1-30 µg/mL, and recovery rates of SPI and CAN from the different skin layers exceeded 85%. The method was not only sensitive (LOD of 0.05 and 0.375 µg/mL and LOQ of 0.157 and 1.139 µg/mL for SPI and CAN, respectively) but also selective against skin matrices and highly representative components of topical formulations. The method moreover demonstrated SPI's degradation in iontophoresis by applying Pt-AgCl electrodes and its continued drug stability using Ag-AgCl electrodes. Altogether, the method proved valuable for quantifying SPI and CAN and may be applied in developing and controlling the quality of dermatological products.
Assuntos
Canrenona/análise , Fármacos Dermatológicos/análise , Iontoforese/métodos , Pele/química , Espironolactona/análise , Animais , Canrenona/química , Canrenona/farmacocinética , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacocinética , Estabilidade de Medicamentos , Excipientes , Limite de Detecção , Modelos Lineares , Nanopartículas , Reprodutibilidade dos Testes , Pele/metabolismo , Absorção Cutânea , Espironolactona/química , Espironolactona/farmacocinética , SuínosRESUMO
Novel protamine-based nanosystems have been studied for cyclosporine-A (CsA) skin delivery. Core-shell structure systems have been developed to this end. These vehicles have particles sizes of 200-300 nm, a low polydispersity index and a zeta potential which varies between -16 mV and +35 mV. The resulting four nanosystems efficiently encapsulated CsA in their oily nucleus (60-80%) and released this drug in a controlled manner. These formulations have shown a high stability in aqueous suspension in storage conditions at 4 °C (for at least 21 months) and in acetate buffer at a physiological temperature of 37 °C (for at least 24 h). Ex vivo transdermal diffusion experiments using Franz diffusion cells and 2- to 3-day-old pig skin as a biological barrier were performed. All nanoformulations designed produced an increase in CsA transdermal delivery and two of these nanosystems presented a marked promoting effect; the more relevant parameters were smaller particle size (200 ± 7 nm) and negative superficial charge. Finally, the ability of these nanosystems to enhance retention of CsA in the skin was also studied. The protamine disposition in the shell influenced CsA skin retention. Therefore, the incorporation of CsA into the nanosystems studied here makes them suitable vehicles for CsA transdermal administration.
Assuntos
Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacocinética , Nanocápsulas/química , Protaminas/química , Absorção Cutânea , Administração Cutânea , Animais , Ciclosporina/química , Fármacos Dermatológicos/química , Emulsões/química , Tamanho da Partícula , Pele/metabolismo , SuínosRESUMO
Bacterial cellulose/carboxymethylcelullose (BC/CMC) biocomposites with different DS-CMC (DS from 0.7 to 1.2) were developed in order to evaluate their impact as a drug delivery system. Biocomposites were loaded with methotrexate (MTX) as an alternative for the topical treatment of psoriasis. Scanning electron microscopy and atomic force microscopy showed that the CMC coated the cellulose nanofibers, leading to the decrease of the elastic modulus as the DS of CMC increased. BC/CMC0.9 exhibited the lower liquid uptake (up to 11 times lower), suggesting that the more linear structure of the intermediate substitute CMC grade (0.9) was able to interact more strongly with BC, resulting in a denser structure. All samples showed a typical burst release effect in the first 15min of test, however the BC/CMC0.9 biocomposite promoted a slight lowering of MTX release rates, suggesting that the DS of CMC can be considered the key factor to modulate the BC properties.
Assuntos
Materiais Biocompatíveis/química , Carboximetilcelulose Sódica/química , Fármacos Dermatológicos/química , Liberação Controlada de Fármacos , Gluconacetobacter xylinus/metabolismo , Metotrexato/química , Nanofibras/química , Meios de Cultura/química , Sistemas de Liberação de Medicamentos , Módulo de Elasticidade , Gluconacetobacter xylinus/crescimento & desenvolvimento , Porosidade , Solubilidade , Engenharia TecidualRESUMO
CONTEXT: Croton sp. are plants with a well-reported antimicrobial activity. Croton limae A.P. Gomes, M.F. Sales P.E. Berry (Euphorbiaceae), known as 'marmeleiro-prateado', is commonly used to manage abdominal pain in Brazil. OBJECTIVE: This work evaluates the phytochemical composition, antimicrobial and modulatory activities of the essential oil of C. limae leaves (EOCL). MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and the modulation of the antibiotic activity were determined using a microdilution method. The concentration of EOCL ranged between 512 and 8 µg/mL. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Candida tropicalis, C. krusei and C. albicans strains were used in the MIC and modulation assays. The antibiotics, amikacin, gentamicin and neomycin, and the antifungals, amphotericin B, benzoylmetronidazole and nystatin, were used in concentrations ranging between 2500 and 2.5 µg/mL. The phytochemical analysis of the EOCL was performed through gas chromatography coupled to a mass spectrometer (GC/MS). RESULTS: Only Staphylococcus aureus was inhibited by a clinically relevant concentration of EOCL (MIC 512 µg/mL). Synergism between the EOCL and amikacin against S. aureus (9.76 µg/mL) and E. coli (39.062 µg/mL); neomycin against E. coli (2.44 µg/mL); and benzoylmetronidazole against C. krusei (256 µg/mL) were observed. The GC/MS analysis identified cedrol, eucalyptol and α-pinene as the main compounds of EOCL. CONCLUSION: EOCL inhibited the growth of S. aureus and potentiated the antibiotic and antifungal effects of drugs against all bacterial and Candida strains, respectively.
Assuntos
Antibacterianos/química , Antifúngicos/química , Óleo de Cróton/química , Croton , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Óleo de Cróton/isolamento & purificação , Óleo de Cróton/farmacologia , Fármacos Dermatológicos/química , Fármacos Dermatológicos/isolamento & purificação , Fármacos Dermatológicos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Folhas de Planta , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
AIM AND OBJECTIVE: Caffeic acid (CA) is a cinnamic acid derivative, found in many vegetable products, with powerful antioxidant activity, the ability to increase collagen production and capacity to prevent premature aging of the skin. The classic emulsions of CA are widely used by the consumer to provide a pleasant, refreshing sensorial experience; however, preparations developed in the form of dry film are presented as a technological alternative due to its facile and safe transportation. The aim of this study was to evaluate the release, permeation, and retention of CA in a film and emulsion through in vitro experiments. MATERIAL AND METHODS: The release evaluation of CA from the emulsion and the film was performed using modified Franz diffusion cells, with an area of 1.77 cm², using Microette equipment (Hanson Research) with a cellulose membrane. The evaluation of the permeation of CA from the formulations was conducted using a similar technique of release, except that a biological membrane was used. RESULTS: High release of active compound and reduced permeation was observed, indicating that CA was able to be retained in the epidermis/dermis, where it should have the desired action. The concentration of caffeic acid in the skin was higher for the film formulation than for the emulsion. This demonstrates a greater efficiency of this type of innovative release system, besides its facile and safe transportation. CONCLUSION: The formulations tested in this paper can release caffeic acid with a Higuchi kinetic profile, in which release of active ingredient occurs by a diffusion process. The film formulations exhibited a lower permeation rate and higher retention in the skin, which is essential for a cosmetic product. The concentration of CA in the skin was also higher for the film formulation when compared to the emulsion. This demonstrates a greater efficiency of this type of innovative release system, in addition to its easy and safe transportation. Therefore, it is possible to suggest CA as a promising substance for dermal use due to its antioxidant, anti-inflammatory, antimicrobial, and collagen production stimulating activity.
Assuntos
Ácidos Cafeicos/farmacologia , Fármacos Dermatológicos/farmacologia , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/química , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/química , Composição de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Pele/efeitos dos fármacosRESUMO
In the context of developing a new natural product-based cosmetic, the in vitro efficacy and safety evaluations of a complex botanical mixture based on Eugenia dysenterica leaf hydroalcoholic extract (EDE) (2.5-1000µg/mL) were carried out. Chromatographic analysis demonstrated the presence of the tannin (ellagic acid) and flavonoids (quercetin and gallic acid) which characterize the EDE as a polyphenol-rich mixture. Using HFF-1 fibroblasts, it was shown that EDE promoted cell regeneration after UVA exposure. It also led to the inhibition of the collagenase, elastase and tyrosinase enzymes, which are involved in skin-related disorders. In terms of toxicological evaluation, the EDE was classified as non-phototoxic through the 3T3 Neutral Red Uptake Phototoxicity Test (OECD N° 432, 2004) and non-eye irritant by Bovine Corneal Opacity and Permeability (OECD N° 437, 2013) assay, in conjunction with corneal histomorphometric analysis. Furthermore, the EDE has no skin sensitization potential as demonstrated by a two-out-of-three prediction model [protein-binding/haptenization (OECD N° 442C, 2015), keratinocyte and dendritic cell activations]. In addition, it was shown that the EDE seems to be non-genotoxic through the cytokinesis-block micronucleus assay (OECD N° 487, 2014) using HepG2 cells. When considered together, these findings support the use of EDE botanical mixture in cosmetic/pharmaceutical products.