Publication: Sistemas multiparticulares para la vectorización de gatifloxacino en el tratamiento de la tuberculosis
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2017-07-14
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Universidad Complutense de Madrid
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Abstract
La tuberculosis (TB) es una enfermedad infecciosa causada por el bacilo Mycobaterium tuberculosis. La bacteria se localiza principalmente en pulmón, TB pulmonar, aunque también puede afectar a otras zonas desarrollándose la TB cerebral. El alto porcentaje de efectos adversos de los tratamientos actuales y la extensa duración de los mismos, han llevado a una baja adherencia al tratamiento por parte de los pacientes desarrollándose resistencias y dando lugar al fracaso terapéutico. Por ello, esta patología constituye un auténtico problema de salud pública. OBJETIVO El objetivo general de la tesis doctoral es mejorar los tratamientos de la TB mediante la vectorización de GAT al lugar de acción. Para ello, se han desarrollados dos sistemas multipartículares biodegradables. Uno de ellos corresponde BHE, útiles para el tratamiento de la TBcerebral. El otro sistema, consiste en una formulación de microesferas biodegradables de PLGA con GAT para ser administradas por vía pulmonar, capaz de acceder a los macrófagos alveolares, actuando directamente en el reservorio del Mycobacterium tuberculosis. Con esta formulación se pretende reducir las resistencias y efectos adversos, acortar la duración del tiempo de tratamiento y disminuir las dosis...
Tuberculosis (TB) is a highly contagious infection caused by M. tuberculosis. TB appears mainly in the lungs but can also develop as extrapulmonary tuberculosis in the central nervous system (CNS). The control of resistant TB represents an important challenge; the downside of currently treatment is mainly due to patient noncompliance which is attributed to the long treatment, high rate of adverse effect due to non-specific distribution. Despite global TB eradication efforts, it is still a global public health concern. OBJETIVE The main objective of this doctoral thesis is the development of two controlled delivery system of gatifloxacin (GAT) to enhance the currently treatment of TB disease targeting the drug directly in the site of action. Biodegradable nanoparticles (NPs) have been developed to cross BBB in order to treat cerebral tuberculosis. The other therapeutic system consists of biodegradable microspheres (MPs); it has been developed in order to uptake by alveolar macrophages for pulmonary TB. This formulation could achieve high intracellular drug concentration in macrophages and would reduce side effects associated with long-term systemic/oral antitubercular therapy. Thereby, it could reduce the duration of treatment and prevent the multi-drug resistance...
Tuberculosis (TB) is a highly contagious infection caused by M. tuberculosis. TB appears mainly in the lungs but can also develop as extrapulmonary tuberculosis in the central nervous system (CNS). The control of resistant TB represents an important challenge; the downside of currently treatment is mainly due to patient noncompliance which is attributed to the long treatment, high rate of adverse effect due to non-specific distribution. Despite global TB eradication efforts, it is still a global public health concern. OBJETIVE The main objective of this doctoral thesis is the development of two controlled delivery system of gatifloxacin (GAT) to enhance the currently treatment of TB disease targeting the drug directly in the site of action. Biodegradable nanoparticles (NPs) have been developed to cross BBB in order to treat cerebral tuberculosis. The other therapeutic system consists of biodegradable microspheres (MPs); it has been developed in order to uptake by alveolar macrophages for pulmonary TB. This formulation could achieve high intracellular drug concentration in macrophages and would reduce side effects associated with long-term systemic/oral antitubercular therapy. Thereby, it could reduce the duration of treatment and prevent the multi-drug resistance...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Farmacia y Tecnología Farmacéutica, leída el 22/06/2016