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Pharm Dev Technol ; 21(5): 554-62, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26024238

RESUMO

CONTEXT: Although several formulation strategies have been developed for the treatment of psoriasis, there is an unmet need for optimization of its therapy. OBJECTIVE: The objective was to develop a nanogel composed of methotrexate (MTX)-loaded nanostructured lipid carrier (MTX-NLC) and to evaluate its potential in imiquimod-induced psoriasis model to ameliorate symptoms of psoriasis. MATERIALS AND METHODS: MTX-NLC nanogel was prepared by hot-homogenization method and optimized by Design of Experiments. Particle size, polydispersity index (PDI) and entrapment efficiency were selected as the critical quality attributes. Antipsoriatic potential of MTX-NLC nanogel was evaluated by Psoriatic Area and Severity Index (PASI) score and histopathological examination in the imiquimod-induced psoriasis model. RESULTS AND DISCUSSION: Optimized MTX-NLC exhibited particle size of 278 ± 10 nm, PDI of 0.231 ± 0.05 and EE of 22.29 ± 1.23%. At the end of 48 h, MTX-NLC gel exhibited slow and prolonged release of MTX (47.32 ± 0.94% versus 94.23 ± 0.79%) compared to MTX gel. Furthermore, it significantly reduced the PASI score with recovery of normalcy of the mice's skin, while the MTX gel exhibited signs of hyper and parakeratosis at the end of the study. CONCLUSION: The developed MTX-NLC gel formulation can be a promising alternative to existing MTX formulation in treating psoriasis.


Assuntos
Metotrexato/administração & dosagem , Metotrexato/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoimina/administração & dosagem , Polietilenoimina/química , Psoríase/tratamento farmacológico , Absorção Cutânea/efeitos dos fármacos , Administração Tópica , Animais , Química Farmacêutica , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Metotrexato/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanogéis , Polietilenoglicóis/metabolismo , Polietilenoimina/metabolismo , Psoríase/metabolismo , Psoríase/patologia , Distribuição Aleatória , Absorção Cutânea/fisiologia , Resultado do Tratamento
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