Aproximaciones al diseño de copolímeros anfifílicos con potencial aplicación en la encapsulación y liberación de Anfotericina B

dc.contributorPérez Pérez, León Darío
dc.contributorGrupo de Investigación en Macromoléculas
dc.creatorRodríguez Molina, Yeimy Johana
dc.date.accessioned2020-03-06T19:35:21Z
dc.date.available2020-03-06T19:35:21Z
dc.date.created2020-03-06T19:35:21Z
dc.date.issued2019-07-19
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/75949
dc.description.abstractEn este estudio, se describe la síntesis de copolímeros anfifílicos de PEG-b-PCL bioconjugados con colesterol o retinol del tipo AB y ABA a través de polimerización por apertura de anillo (ROP) y esterificación de Steglich. La copolimerización fue confirmada empleando resonancia magnética nuclear protónica (RMN1H), espectroscopia infrarroja (FTIR) y cromatografía de permeación en gel (GPC), las propiedades térmicas fueron estudiadas por calorimetría diferencial de barrido (DSC). Posteriormente, se realizó el estudio de las relaciones entre las propiedades coloidales de las micelas y los copolímeros anfifílicos sintetizados. La micelización de los copolímeros y su concentración micelar critica (CMC) se estudió empleando el método de fluorescencia con pireno. De acuerdo con los resultados, se evidencia que los métodos de polimerización y bioconjugación empleados dieron lugar a copolímeros con entidades terpénicas enlazadas covalentemente a su estructura. Por su parte, las propiedades coloidales de las micelas evidencian que el incremento del segmento hidrofóbico de los materiales genera disminución en la CMC, conveniente para la estabilidad de las dispersiones micelares empleadas en la liberación controlada de fármacos. Adicionalmente, se caracterizaron los sistemas micelares empleando DLS, potencial Z y TEM, en su orden, se obtuvieron partículas micelares de tamaños que comprenden el rango entre 22,0 y 136,8 nm; la estabilización de los sistemas micelares establecida por el potencial Z es de tipo estérico, teniendo en cuenta que la carga de las partículas fue cercana a cero; En tanto, la morfología de las micelas mostrada en las imágenes TEM confirma la presencia de partículas nanométricas con estructura tipo “core-shell”. Finalmente, se evaluó la potencial aplicación de estos copolímeros bioconjugados en la encapsulación de AmB, el estudio de su liberación controlada y el efecto sobre el estado de agregación en cada sistema micelar cargado con AmB. Se evidenció que las unidades de terpeno inciden favorablemente en la encapsulación de AmB, encontrándose mayores contenidos de fármaco cuando se bioconjugan con retinol (10,21%). No obstante, la conjugación con colesterol también incrementa la solubilización de AmB (5,88%) con respecto a los copolímeros blanco (<3,16%). Los estudios de liberación demuestran condiciones controladas y porcentajes de liberación menores en los copolímeros bioconjugados con terpenos, corroborando que el núcleo micelar genera un microambiente con interacciones favorables que retardan la salida de AmB al medio de liberación. Finalmente, los estudios de agregación realizados por espectrofotometría UV-Vis, demostraron que la AmB cargada en las micelas se encuentra formando autoagregados.
dc.description.abstractIn this study, the synthesis of amphiphilic PEG-b-PCL copolymers type AB and ABA bioconjugate with cholesterol or retinol through ring open polymerization (ROP) and Steglich esterification are described. The copolymerization was confirmed using proton nuclear magnetic resonance (¹H NMR) and infrared spectroscopy (FTIR) and gel permeation chromatography (GPC), the thermal properties were studied using differential scanning calorimetry (DSC). Then, the study of the relationship between the colloidal properties of the micelles and the amphiphilic copolymers synthetized were carry out. The copolymers micellization and its critical micelle concentration (CMC) were perform using fluorescence method with pyrene. According to the results, it is evident that the polymerization and bioconjugate methods used gave rise to copolymers with terpene entities covalently linked to its structure. In the same way, the colloidal properties of the micelles show that an increase in the hydrophobic segment of the material generates a CMC decrease; this is convenient for the stability of the micellar dispersion used in drugcontrolled release. The micellar systems were characterized employing Dynamic Light Scattering (DLS), Z potential and transmission electron microscopy (TEM). In its order, micellar particles of sizes that comprise the range between 22,0 and 136.8 nm were obtained; the stabilization of the micellar systems stablished using Z potential exhibit a steric type, taking in account that the particle charge was near to cero. While, the morphology shown in TEM images confirm the presence of nanometric core-shell type particles. The application of this bioconjugate copolymers in the AmB encapsulation, the study of their controlled release and the aggregation state were evaluated for each micellar system charged with AmB. It was evidenced that the terpene units favorably affect the encapsulation of AmB, when the AmB was bioconjugate with retinol the obtained drug content was 10,21%. However, the conjugation with cholesterol increase also the AmB solubilization (5,88%) compared to blank copolymers (<3,16%). Release studies demonstrate controlled conditions and lower release rates in bioconjugate copolymers with terpenes, this confirms that the micellar core generates a microenvironment with favorable interactions that delay the exit of AmB to the release medium. Finally, aggregation studies performed by UV-Vis spectrophotometry showed that the AMB loaded in the micelles is arranged in self-aggregates form.
dc.languagespa
dc.publisherDepartamento de Química
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
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dc.titleAproximaciones al diseño de copolímeros anfifílicos con potencial aplicación en la encapsulación y liberación de Anfotericina B
dc.typeOtro


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