Diseño de nanomateriales biocompatibles en base a nanoesferas de sílica y nanovarillas de alúmina para liberación controlada de doxorrubicina.
No Thumbnail Available
Date
2022
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad de Concepción
Abstract
Aumentar la biocompatibilidad de nanomateriales y modificar el comportamiento de la cinética de liberación de fármacos poco solubles es un desafío de la comunidad científica. Particularmente en la última década materiales a escala nanométrica presentan un elevado potencial como carrier de sustancias activas para fines biomédicos. Es por esto, que, la administración controlada de fármacos para tratar tejidos enfermos se presenta como una de las técnicas más prometedoras. No obstante, estas estrategias requieren un diseño racional que permitan mejorar la eficiencia y controlar la liberación del principio activo. En este trabajo de tesis se estudió la liberación controlada del fármaco anticancerígeno doxorrubicina (DOX) utilizando nanoesferas de sílica mesoporosas (MSN) y nanovarillas de alúmina (ANW) modificadas superficialmente con polietilenglicol metil éter (PEG). Para esto, los nanomateriales se sintetizaron y se modificaron covalentemente con PEG de 550 Da y 2000 Da, respectivamente. obteniendo 6 grupos experimentales, MSN prístina, 2 diferentes MSN-PEG, ANW prístina y 2 diferentes ANW-PEG. Todos los sistemas fueron caracterizados por técnicas fisicoquímicas, posteriormente cargados con DOX y se estudió la cinética de liberación del fármaco en medio fisiológico simulado. Se evaluó la biocompatibilidad de los materiales realizando ensayos de hemólisis, ensayo de interacción con proteínas del suero y viabilidad celular. Los resultados sugieren que los nanomateriales tienen diferencias en la capacidad de adsorción y liberación de DOX, y también, se observó una discrepancia en la cinética de la liberación entre los materiales prístinos y modificados superficialmente con PEG. Lo anterior se atribuye a la que la presencia del PEG en la superficie modifica la liberación de la DOX al medio líquido. La biocompatibilidad de los sistemas modificados con PEG aumentaron con respecto a los prístinos y los nanomateriales fueron capaces de disminuir la viabilidad celular de una línea celular cancerígena únicamente cuando están cargados con DOX.
Increasing the biocompatibility of nanomaterials and modifying the behavior of the release kinetics of poorly soluble drugs is a challenge for the scientific community. Particularly, in the last decade, materials at the nanometric scale have great potential as carriers of active substances for biomedical purposes. For this reason, the controlled administration of drugs to treat diseased tissues is presented as one of the most promising techniques. However, these strategies require a rational design to improve efficiency and control the release of the active ingredient. In this work, the controlled release of the anticancer drug doxorubicin (DOX) was studied using mesoporous silica nanospheres (MSN) and alumina nanowires (ANW). Both nanomaterials were surface modified by covalently bonding with polyethylene glycol methyl ether (PEG) at 550 Da and 2000 Da of molecular weight obtaining 6 experimental groups: pristine MSN, 2 different MSN-PEG, pristine ANW, and 2 different ANW-PEG. All the systems were characterized by physicochemical techniques, then loaded with DOX and their drug release kinetic in physiologic simulated medium was studied. Likewise, the biocompatibility of the materials was evaluated by carrying out hemolysis tests, non-specific proteins adsorption and cell viability test. The results suggest that nanomaterials have differences in DOX adsorption and release capacity, and a discrepancy in release kinetics was observed between pristine and PEG-surface-modified materials. This trend is attributed to the presence of PEG, which modified the diffusion of the drug from the surface to the liquid in the DOX release. The biocompatibility of the PEG modified systems increased with respect to the pristine ones and the nanomaterials were able to decrease the cell viability of a cancer cell line only when loaded with DOX.
Increasing the biocompatibility of nanomaterials and modifying the behavior of the release kinetics of poorly soluble drugs is a challenge for the scientific community. Particularly, in the last decade, materials at the nanometric scale have great potential as carriers of active substances for biomedical purposes. For this reason, the controlled administration of drugs to treat diseased tissues is presented as one of the most promising techniques. However, these strategies require a rational design to improve efficiency and control the release of the active ingredient. In this work, the controlled release of the anticancer drug doxorubicin (DOX) was studied using mesoporous silica nanospheres (MSN) and alumina nanowires (ANW). Both nanomaterials were surface modified by covalently bonding with polyethylene glycol methyl ether (PEG) at 550 Da and 2000 Da of molecular weight obtaining 6 experimental groups: pristine MSN, 2 different MSN-PEG, pristine ANW, and 2 different ANW-PEG. All the systems were characterized by physicochemical techniques, then loaded with DOX and their drug release kinetic in physiologic simulated medium was studied. Likewise, the biocompatibility of the materials was evaluated by carrying out hemolysis tests, non-specific proteins adsorption and cell viability test. The results suggest that nanomaterials have differences in DOX adsorption and release capacity, and a discrepancy in release kinetics was observed between pristine and PEG-surface-modified materials. This trend is attributed to the presence of PEG, which modified the diffusion of the drug from the surface to the liquid in the DOX release. The biocompatibility of the PEG modified systems increased with respect to the pristine ones and the nanomaterials were able to decrease the cell viability of a cancer cell line only when loaded with DOX.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Óxido de Aluminio, Cinética, Hemólisis, Mitosis, Nanotecnología, Medicamentos