Sistemas nanoestruturados mucoadesivos para administração nasal de zidovudina
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Data
2012-08-31
Autores
Carvalho, Flávia Chiva [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A zidovudina (AZT) é o fármaco de primeira escolha no tratamento da AIDS, mas sofre metabolismo pré-sistêmico e possui efeitos adversos dose-dependentes. A via nasal é uma alternativa que pode promover a rápida absorção do fármaco e evitar o metabolismo pré-sistêmico. Porém, ela possui mecanismos de depuração mucociliar que pode eliminar rapidamente a formulação da cavidade nasal. Sistemas de liberação mucoadesivos podem aumentar a fixação da formulação, controlar e aumentar a absorção de fármacos através da mucosa nasal. Sistemas compostos por tensoativos podem formar estruturas líquido-cristalinas in situ e promover a mucoadesão. O objetivo deste trabalho foi desenvolver sistemas precursores de cristais líquidos compostos pelo tensoativo álcool cetílico etoxilado 20 OE e propoxilado 5 OP (PPG-5-CETETH-20) para administração nasal do AZT. O comportamento de fases dos sistemas foi investigado pela construção de diagramas de fases binários e ternários combinando o tensoativo com água e fosfatidilcolina ou ácido oleico. As amostras escolhidas foram caracterizadas por microscopia de luz polarizada (MLP), reologia, análise mecânica e de obtenção da força mucoadesiva utilizando texturômetro. Foram realizados estudos de permeação ex vivo e testes pré-clínicos em ratos. Os resultados mostram que é possível obter um sistema composto por PPG-5-CETETH-20/ ácido oleico/água com escoamento adequado para administração nasal e alta capacidade de solubilização do AZT. A mistura do sistema com muco artificial forma uma matriz líquido-cristalina com características reológicas, perfil de textura e força mucoadesiva adequados para promover a mucoadesão na cavidade nasal. O ensaio de permeação utilizando...
Zidovudine (AZT) is the first choice drug for AIDS treatment, but it undergoes presystemic metabolism and exhibits dose-dependent side effects. The nasal route is an alternative that promotes the rapid absorption of the drug and avoids its presistemic metabolism. However, the mucociliary clearance mechanism can rapidly eliminate the formulation from the nasal cavity. Mucoadhesive drug delivery systems may raise the fixation of the formulation, control and increase AZT absorption through the nasal mucosa. Systems composed of surfactants can form in situ liquid crystalline structures and promote the mucoadhesion. The objective of this work was to develop liquid crystal precursor systems composed of the surfactant polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20) for the nasal administration of AZT. The phase behavior of the systems was investigated by the construction of binary and ternary phase diagrams combining the surfactant with water, phosphatidylcholine or oleic acid. The chosen samples were characterized by polarized light microscopy (PLM), rheology, and mechanical analysis and by obtation of the mucoadhesive force using a texturometer. It was performed ex vivo drug permeation studies and pre-clinical tests in rats. The results showed that it is possible to obtain a liquid system composed of PPG-5-CETETH-20/ oleic acid/ water with high capacity for AZT solubilization. The mixture of the system with artificial mucus forms a liquid crystalline matrix with suitable rheological characteristics, texture profile and mucoadhesive force for promoting the mucoadhesion in the nasal cavity. The permeation assay using porcine nasal mucosa showed that the formulation does not retain AZT release and increases the flux J (0.871 g/min.cm) and the permeability coefficient Kp... (Complete abstract click electronic access below)
Zidovudine (AZT) is the first choice drug for AIDS treatment, but it undergoes presystemic metabolism and exhibits dose-dependent side effects. The nasal route is an alternative that promotes the rapid absorption of the drug and avoids its presistemic metabolism. However, the mucociliary clearance mechanism can rapidly eliminate the formulation from the nasal cavity. Mucoadhesive drug delivery systems may raise the fixation of the formulation, control and increase AZT absorption through the nasal mucosa. Systems composed of surfactants can form in situ liquid crystalline structures and promote the mucoadhesion. The objective of this work was to develop liquid crystal precursor systems composed of the surfactant polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20) for the nasal administration of AZT. The phase behavior of the systems was investigated by the construction of binary and ternary phase diagrams combining the surfactant with water, phosphatidylcholine or oleic acid. The chosen samples were characterized by polarized light microscopy (PLM), rheology, and mechanical analysis and by obtation of the mucoadhesive force using a texturometer. It was performed ex vivo drug permeation studies and pre-clinical tests in rats. The results showed that it is possible to obtain a liquid system composed of PPG-5-CETETH-20/ oleic acid/ water with high capacity for AZT solubilization. The mixture of the system with artificial mucus forms a liquid crystalline matrix with suitable rheological characteristics, texture profile and mucoadhesive force for promoting the mucoadhesion in the nasal cavity. The permeation assay using porcine nasal mucosa showed that the formulation does not retain AZT release and increases the flux J (0.871 g/min.cm) and the permeability coefficient Kp... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Cristais líquidos, Mucosa nasal, Farmacocinetica, Microscopia, Aids - Tratamento
Como citar
CARVALHO, Flávia Chiva. Sistemas nanoestruturados mucoadesivos para administração nasal de zidovudina. 2012. 163 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2012.