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Caracterización de copolímeros en bloque conjugados como vehículos nanoestructurados para Anfotericina B

dc.contributor.advisorPérez Pérez, León Daríospa
dc.contributor.authorArias Patrón, Elsa Ruthspa
dc.contributor.researchgroupGrupo de Investigación en Macromoléculasspa
dc.date.accessioned2020-08-18T16:27:45Zspa
dc.date.available2020-08-18T16:27:45Zspa
dc.date.issued2020-04-07spa
dc.description.abstractLa Anfotericina B (AmB) es un antifúngico de amplio espectro de acción, su actual administración se encuentra limitada por su toxicidad relacionada con su autoagregación al ser una molécula anfifílica. El uso de micelas poliméricas constituye una alternativa promisoria como vehículo de AmB con toxicidad reducida. Sin embargo, los sistemas micelares reportados en la literatura muestran interacciones débiles con la AmB, originando bajos porcentajes de encapsulación y altas velocidades de liberación. En la presente investigación se caracterizaron sistemas de entrega micelar bioinspirados para AmB basados en polietilenglicol (PEG), policaprolactona (PCL) y 5-metil-5-propargiloxicarbonil-1,3-dioxan-2-ona (MCP), modificados con biomoléculas como colesterol, ácido oleico y 1,2-distearoil-sn-glicero-3-fosfoetanolamina (DSPE). Para tal fin, se estudió su capacidad de solubilizar, el estado de agregación, los perfiles de liberación y la concentración mínima inhibitoria (CMI) de los sistemas micelares. Del mismo modo se estudiaron sus propiedades térmicas y morfológicas. Se comprobó que existe una estrecha relación entre la composición química de los materiales poliméricos y su desempeño como vehículos nanoestructurados de AmB. La conjugación de dichos materiales con biomoléculas como DSPE incrementó la capacidad de encapsulación del fármaco hasta un 20%. Se determinó que segmentos de PCL cortos favorecen la encapsulación de AmB. Las formulaciones estudiadas permitieron una liberación controlada con porcentajes de liberación cercanos al 10% transcurridas 6 horas. Se logró disminuir los valores de CMI en comparación a los obtenidos para la formulación comercial de AmB (Fungizone ®). En conclusión, los materiales bioinspirados diseñados pueden ser empleados como vehículos nanoestructurados de fármacos como la AmB.spa
dc.description.abstractAmphotericin B (AmB) is a broad-spectrum antifungal, its current administration is limited by its toxicity related to its self-aggregation as it is an amphiphilic molecule. The use of polymeric micelles constitutes a promising alternative as an AmB vehicle with reduced toxicity. However, the micellar systems reported in the literature show weak interactions with AmB, resulting in low encapsulation percentages and high release rates. In the present investigation, bioinspired micellar delivery systems for AmB protocols were characterized in polyethylene glycol (PEG), polycaprolactone (PCL) and 5-methyl-5-propargiloxycarbonyl-1,3-dioxan-2-one (MCP), modified with biomolecules such as cholesterol, oleic acid and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE). To this end, their ability to solubilize, the state of aggregation, release profiles and minimum inhibitory concentration (MIC) of the micellar systems was studied. In the same way its thermal and morphological properties were studied. It is proven that there is a close relationship between the chemical composition of polymeric materials and their performance as nanostructured AmB vehicles. The conjugation of these materials with biomolecules such as DSPE increased the encapsulation capacity of the drug up to 20%. It was determined that short PCL segments favor the encapsulation of AmB. The formulations studied allowed a controlled release with release rates close to 10% after 6 hours. The MIC values were reduced compared to the results for the commercial formulation of AmB (Fungizone ®). In conclusion, the proposed bioinspired materials can be used as nanostructured vehicles for drugs such as AmB.spa
dc.description.additionalLínea de Investigación: Copolímeros funcionalesspa
dc.description.degreelevelMaestríaspa
dc.format.extent105spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/78067
dc.language.isospaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Químicaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Químicaspa
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dc.rightsDerechos reservados - Universidad Nacional de Colombiaspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.rights.spaAcceso abiertospa
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.ddc540 - Química y ciencias afinesspa
dc.subject.ddc547 - Química orgánicaspa
dc.subject.proposalmicela poliméricaspa
dc.subject.proposalpolymeric micelleeng
dc.subject.proposalanfotericina Bspa
dc.subject.proposalamphotericin Beng
dc.subject.proposalpolietilenglicolspa
dc.subject.proposalpolyethylene glycoleng
dc.subject.proposalpolycaprolactoneeng
dc.subject.proposalpolicaprolactonaspa
dc.subject.proposalaggregationeng
dc.subject.proposalcopolímeros en bloquespa
dc.subject.proposalencapsulaciónspa
dc.subject.proposalencapsulationeng
dc.titleCaracterización de copolímeros en bloque conjugados como vehículos nanoestructurados para Anfotericina Bspa
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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