Vectorización de agentes terapéuticos a macrófagos para el tratamiento de procesos inflamatorios
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2024
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12/07/2023
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Universidad Complutense de Madrid
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Abstract
La inflamación es una respuesta inmediata e inespecífica con la que el organismo responde ante una agresión química, física o biológica. Si la inflamación se prolonga en el tiempo, puede provocar daño tisular. Entre las patologías que cursan con inflamación se encuentran la artritis reumatoide (AR) y la COVID-19. La sulfasalazina (SSZ) es un antiinflamatorio no esteroideo (AINE) con propiedades antiinflamatorias e inmunosupresora. Es uno de los fármacos antirreumáticos modificadores de la enfermedad ampliamente empleado en el tratamiento de la AR. El celecoxib (CXB) es un AINE con actividad antiinflamatoria, analgésica y antipirética que ha mostrado ser eficaz para el tratamiento de la COVID-19. En esta enfermedad los pulmones son los órganos más frecuentemente afectados y, por tanto, una interesante diana terapéutica. La vectorización de antiinflamatorios a macrófagos es una estrategia tecnológica que permite reducir los efectos adversos asociados a la biodistribución no selectiva de la SSZ y CXB. Estos agentes pueden ir encapsulados en micropartículas (MPs) capaces de ser captadas por el sistema fagocítico mononuclear. Para que las MPs, sean captadas por macrófagos, deben presentan unas características adecuadas en su tamaño y composición. Tras la internalización en estas células el fármaco incorporado se libera de manera controlada, focalizando el activo en el sitio de acción...
Inflammation is an immediate and non-specific response that the body initiates when there is a chemical, physical, or biological aggression. If the inflammation persists over time, it can lead to tissue damage. Some of the pathologies that involve inflammation include rheumatoid arthritis (RA) and COVID-19. Sulfasalazine (SSZ) is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory and immunosuppressive properties. It is one of the disease-modifying antirheumatic drugs widely used in the treatment of RA. Celecoxib (CXB) is an NSAID with anti-inflammatory, analgesic, and antipyretic activity that has shown to be effective in the treatment of COVID-19. In this disease, the lungs are the organs most frequently affected and, therefore, an interesting therapeutic target. The controlled delivery of anti-inflammatory drugs to macrophages is a technological strategy that allows the reduction of adverse effects associated the non-selective biodistribution of SSZ and CXB. These agents can be encapsulated in microparticles (MPs) capables of being uptaken by the mononuclear phagocytic system. For the uptake of MPs by macrophages, MPs must have appropriate characteristics in size and composition. After internalization into these cells, the drug is controlled released from MPs, focusing the active agent at the site of action...
Inflammation is an immediate and non-specific response that the body initiates when there is a chemical, physical, or biological aggression. If the inflammation persists over time, it can lead to tissue damage. Some of the pathologies that involve inflammation include rheumatoid arthritis (RA) and COVID-19. Sulfasalazine (SSZ) is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory and immunosuppressive properties. It is one of the disease-modifying antirheumatic drugs widely used in the treatment of RA. Celecoxib (CXB) is an NSAID with anti-inflammatory, analgesic, and antipyretic activity that has shown to be effective in the treatment of COVID-19. In this disease, the lungs are the organs most frequently affected and, therefore, an interesting therapeutic target. The controlled delivery of anti-inflammatory drugs to macrophages is a technological strategy that allows the reduction of adverse effects associated the non-selective biodistribution of SSZ and CXB. These agents can be encapsulated in microparticles (MPs) capables of being uptaken by the mononuclear phagocytic system. For the uptake of MPs by macrophages, MPs must have appropriate characteristics in size and composition. After internalization into these cells, the drug is controlled released from MPs, focusing the active agent at the site of action...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 12/07/2023