Escalante Castro, Bryan A. (2021) Estudio en microesferas vítreas porosas de SiO_2 para la adsorción y desorción de drogas antineoplásicas. Caso de estudio : carga y descarga de doxorrubicina / Study on SiO_2 porus vitreous microspheres for the adsorption and desorption of antineoplastic drugs. Case study : loading and releasing of doxorubicin. Maestría en Ciencias Físicas, Universidad Nacional de Cuyo, Instituto Balseiro.
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Resumen en español
El objetivo principal de este trabajo consiste en la fabricación y caracterización de microesferas porosas de sílice vítrea y estudios de adsorción y desorción de doxorrubicina en estas. Se fabricó un vidrio por fusión de una mezcla de óxidos y sales de composición nominal 65.6 SiO_2.27.8B_2O_3.6.0 N_a2O.0.6 Al_2O_3 [1] porcentajes peso en peso. Se produjeron microesferas a partir de partículas irregulares de vidrio de tamaño entre 25-35µm por el método de esferoidización por llama. Como resultado se obtuvieron microesferas de supercie y morfología regular. Se obtuvieron microesferas porosas, luego de ser sometidas a un tratamiento térmico de 660ºC durante seis y diez horas . Obteniéndose así dos fases vítreas inmiscibles, una rica en sílice y otra rica en sodio y boro soluble en agua. Seguidamente las microesferas fueron lavadas durante dos y cuatro días, en agua para remover la fase soluble, logrando como producto final microesferas porosas. A partir de SEM se corroboró que este proceso no genera daños en las microesferas y mantienen su morfología regular luego de este proceso. De igual manera a través de SEM se corroboró una diferencia estructural, mayor interconectividad de los poros a mayor tiempo de separación en fases. También se verificó tanto por EDS como XPS que la composición de estas microesferas porosas es mayormente sílice vítrea. Se llevaron acabo estudios de fluorescencia de soluciones de doxorrubicina en agua desionizada y fluido biológico simulado (FBS). Estos demostraron que la fluorescencia de la doxorrubicina no es siempre creciente con la concentración, probablemente asociado a la formación de agrupaciones moleculares. Además, es sensible a la presencia de iones disminuyendo así la intensidad de fluorescencia al estar expuesta a estos. También se logró observar que la emisión de fluorescencia de esta droga es sensible a la temperatura. Se realizaron cargas y liberaciones de doxorrubicina en las microesferas porosas. La cinética de carga en agua desionizada revela una capacidad de aproximadamente el 70% en una solución incubadora de ~900µM y una carga completa en ~55µM. Las microesferas cargadas en ~55µM muestran un liberación en FBS del 70% en 45 min, en el caso de las cargadas en ~900µM decargan aproximadamente este mismo porcentaje en 6.5 horas. Las liberaciones en agua desionizada son más sostenidas en el tiempo, alcanzando hasta un 21% en 10 días continuos. Esto sugiere una fuerte unión del fármaco en el sistema en ausencia de iones; y durante la liberación en FBS una competencia entre los iones y los sitios de adsorción de la droga a las microesferas porosas.
Resumen en inglés
The main objective of this work is the development and characterization of porous microspheres and the study of its load and discharge doxorubicin capacity. A glass was made by melting a mixture of oxides and salts of nominal composition 65.6 SiO_2.27.8B_2O_3.6.0 N_a2O.0.6 Al_2O_3 w/w% [1]. Microspheres were manufactured from irregular glass particles of size between 25-35µm by the ame spheroidization method. As a result, microspheres with a surface and regular morphology were obtained. Porous microspheres were obtained by a thermal separation treatment of 660ºC during six and ten hours. In this way two immiscible glass phases were obtained, one of these is rich in silica, and the other one is rich in boron and sodium. The last one is water soluble. The microspheres were lixiviated during two and four days. The microspheres have no damage, and their regular morphology is maintained after this process. It was observed by SEM a difference in structure, greater interconnectivity of the pores for a greater time in phases separation. It was also veried by EDS and XPS that the composition of these porous microspheres is mostly glass silica. Fluorescence studies of solutions of doxorubicin in deionized water and simulated biological uid (SBF) were carried out. These showed that the uorescence of doxorubicin is not always increasing with concentration, probably associated with the formation of molecular clusters. In addition, it is sensitive to the presence of ions, thus reducing the intensity of uorescence when exposed to them. Doxorubicin loading and releasing were performed on the porous microspheres. Loading kinetics in deionized water reveal a capacity of approximately 70% in a ~900µM incubator solution and a full load in ~55µM. Loaded microspheres in ~55µM show a releasing in SBF about 70% for 45 min, those loaded in ~900µM released about same percentage for 6.5 hours. Releasing in deionized water are more sustained over time, reaching up to 21% in 10 continuous days. This suggests a strong binding of the drug in the system in the absence of ions; and during the releasing in SBF a competition between the ions and the adsorption sites of the drug to the porous microspheres.
| Tipo de objeto: | Tesis (Maestría en Ciencias Físicas) |
|---|---|
| Palabras Clave: | Glass; Vidrio; Microspheres; Microesferas; Leaching; Lixiviación; Silica; Sílice; Doxorubicin; Doxorubicina; [Phase separation; Separación en fases] |
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| Materias: | Biología Ingeniería > Ciencia de los materiales Medicina > Física médica |
| Divisiones: | Gcia. de área de Aplicaciones de la tecnología nuclear > Gcia. de Investigación aplicada > Materiales nucleares > Aplicaciones médicas e industriales |
| Código ID: | 940 |
| Depositado Por: | Marisa G. Velazco Aldao |
| Depositado En: | 16 Jul 2021 11:02 |
| Última Modificación: | 16 Jul 2021 11:02 |
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