Estratégias para modular a permeação cutânea de acetato de dexametasona: avaliação in vitro da permeação e in vivo da atividade anti-nociceptiva
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Data
2016-01-25
Autores
Oyafuso, Márcia Helena [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A administração de compostos na pele é dificultada principalmente pelo estrato córneo; dessa forma diversas técnicas químicas e físicas podem ser exploradas e combinadas de modo a vencer esta barreira. O acetato de dexametasona (DXM) é um potente antiinflamatório utilizado principalmente no tratamento de doenças inflamatórias e autoimunes que, embora muito utilizado, pode promover uma serie de efeitos colaterais sistêmicos. Dessa forma, sua aplicação tópica pode ser conveniente, de forma a localizá-lo no seu sítio de ação. O objetivo deste trabalho foi o desenvolvimento de sistemas líquido-cristalinos (SLC) estabilizados com polioxietileno 20 cetil éter como tensoativo utilizando diferentes fases oleosas: ácido oleico (AO), miristato de isoproprila (MI) e N metil pirrolidona (NMP), e posterior realização de ensaios de permeação cutânea in vitro e atividade anti-noceptiva in vivo. As amostras foram caracterizadas por microscopia de luz polarizada e espalhamento de raios-X a baixo ângulo, as quais resultaram em sistemas líquido-cristalinos de mesofases lamelares e hexagonais; estes sistemas apresentaram (G)’>(G”) nos estudos reológicos, indicando um comportamento predominantemente elástico. O ensaio de perfil de textura revelou que as amostras hexagonais constituídas por NMP e MI foram as que apresentaram maior adesividade e que as amostras lamelares foram mais bioadesivas. Os ensaios de liberação demonstraram que os sistemas lamelares liberaram maior porcentagem de fármaco em relação aos hexagonais . Nos ensaios de permeação cutânea, os resultados revelaram que o fármaco não permeou, porém alcançou a epiderme e derme para as formulações DAO22, DANMP22, DANMP23, DNMP23. O estudo da iontoforese demonstrou que a presença da corrente elétrica foi capaz de impulsionar o fluxo de permeação do fármaco. O ensaio in vivo demonstrou que os sistemas lamelares contendo AO + NMP e os hexagonais com a presença de MI apresentaram maior eficácia anti-nociceptiva comparado à formulação comercial. Sugere-se que os SLC desenvolvidos apresentam potencial para modular a permeação cutânea do DXM e que uso da iontoforese é capaz de aumentar o fluxo da permeação deste fármaco incorporados nos sistemas.
Administration of compounds in the skin is mainly hindered by stratum corneum. Thus, various chemical and physical techniques may be exploited and combined in order to overcome this barrier. Acetate dexamethasone (DXM) is a potent a nti-inflamatory and immunosuppressive primarily used in the treatment of inflammatory, autoimmune and allergic that although widely used, can promote a series of systemic side effects. Thus, topical application may be appropriate in order to find it on their site of action. The objective of this work was to develop liquid crystal systems (LCS) stabilized with polyoxyethylene 20 cetyl ether as surfactant using different oil phases: oleic acid (OA), isopropyl myristate (IM), N methyl pyrrolidone (NMP), and subsequent testing of skin permeation in vitro and in vivo anti-noceptiva activity.The samples were characterized by polarized light microscopy and SAXS, which showed the presence of liquid crystal systems of lamellar mesophases and hexagonal. These systems showed (G)’ > (G”) in rheology studies, indicating a predominantly elastic behavior. The texture profile test revealed that the hexagonal samples containing in its composition NMP and IM showed the highest adhesiveness and that the lamellar samples were more bioadhesive. Release tests showed that the lamellar systems release a higher percentage of drug when compared to the hexagonal systems.In cutaneous permeation tests, the results showed that the drug does not permeate, but reached the epidermis and dermis layers to the formulation (DAO22, DANMP22, DANMP23, DNMP23). The skin permeation with iontophoresis showed the presence of electric current was able to boost the drug permeation flux. The in vivo assay showed that the lamellar systems containing OA + NMP and the hexagonal with the presence of IM had higher antinociceptive effectiveness compared to the commercial formulation. It is suggested that the LCS developed in this work have the potencial to modulate the permeation of DXM and use of iontophoresis is capable of increasing the permeation flux of drug incorporated in the systems.
Administration of compounds in the skin is mainly hindered by stratum corneum. Thus, various chemical and physical techniques may be exploited and combined in order to overcome this barrier. Acetate dexamethasone (DXM) is a potent a nti-inflamatory and immunosuppressive primarily used in the treatment of inflammatory, autoimmune and allergic that although widely used, can promote a series of systemic side effects. Thus, topical application may be appropriate in order to find it on their site of action. The objective of this work was to develop liquid crystal systems (LCS) stabilized with polyoxyethylene 20 cetyl ether as surfactant using different oil phases: oleic acid (OA), isopropyl myristate (IM), N methyl pyrrolidone (NMP), and subsequent testing of skin permeation in vitro and in vivo anti-noceptiva activity.The samples were characterized by polarized light microscopy and SAXS, which showed the presence of liquid crystal systems of lamellar mesophases and hexagonal. These systems showed (G)’ > (G”) in rheology studies, indicating a predominantly elastic behavior. The texture profile test revealed that the hexagonal samples containing in its composition NMP and IM showed the highest adhesiveness and that the lamellar samples were more bioadhesive. Release tests showed that the lamellar systems release a higher percentage of drug when compared to the hexagonal systems.In cutaneous permeation tests, the results showed that the drug does not permeate, but reached the epidermis and dermis layers to the formulation (DAO22, DANMP22, DANMP23, DNMP23). The skin permeation with iontophoresis showed the presence of electric current was able to boost the drug permeation flux. The in vivo assay showed that the lamellar systems containing OA + NMP and the hexagonal with the presence of IM had higher antinociceptive effectiveness compared to the commercial formulation. It is suggested that the LCS developed in this work have the potencial to modulate the permeation of DXM and use of iontophoresis is capable of increasing the permeation flux of drug incorporated in the systems.
Descrição
Palavras-chave
Acetato de dexametosona, Sistemas líquido-cristalinos, Promotores químicos de permeação cutânea, Iontoforese, Inflamação, Modelos animais