Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos
En el presente trabajo de investigación se sintetizó una biblioteca de materiales basados en copolímeros en bloque anfifílicos de composiciones variables empleando monómeros biocompatibles y altamente biodegradables de ε-caprolactona (ε-CL) y 5-metil-5-propargiloxicarbonil-1,3-dioxan-2-ona (MCP). Lo...
- Autores:
-
Angarita Villamizar, Angie Vivian Esther
- Tipo de recurso:
- Work document
- Fecha de publicación:
- 2020
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/77929
- Acceso en línea:
- https://repositorio.unal.edu.co/handle/unal/77929
- Palabra clave:
- 540 - Química y ciencias afines
660 - Ingeniería química
Anfotericina B
copolímeros
policaprolactona
biomoléculas
micelas
Amphotericin B
copolymers
polycaprolactone
biomolecules
micelles
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| title |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| spellingShingle |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos 540 - Química y ciencias afines 660 - Ingeniería química Anfotericina B copolímeros policaprolactona biomoléculas micelas Amphotericin B copolymers polycaprolactone biomolecules micelles |
| title_short |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| title_full |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| title_fullStr |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| title_full_unstemmed |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| title_sort |
Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos |
| dc.creator.fl_str_mv |
Angarita Villamizar, Angie Vivian Esther |
| dc.contributor.advisor.spa.fl_str_mv |
Pérez Pérez, León Darío |
| dc.contributor.author.spa.fl_str_mv |
Angarita Villamizar, Angie Vivian Esther |
| dc.contributor.corporatename.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Investigación en Macromoléculas |
| dc.subject.ddc.spa.fl_str_mv |
540 - Química y ciencias afines 660 - Ingeniería química |
| topic |
540 - Química y ciencias afines 660 - Ingeniería química Anfotericina B copolímeros policaprolactona biomoléculas micelas Amphotericin B copolymers polycaprolactone biomolecules micelles |
| dc.subject.proposal.spa.fl_str_mv |
Anfotericina B copolímeros policaprolactona biomoléculas micelas |
| dc.subject.proposal.eng.fl_str_mv |
Amphotericin B copolymers polycaprolactone biomolecules micelles |
| description |
En el presente trabajo de investigación se sintetizó una biblioteca de materiales basados en copolímeros en bloque anfifílicos de composiciones variables empleando monómeros biocompatibles y altamente biodegradables de ε-caprolactona (ε-CL) y 5-metil-5-propargiloxicarbonil-1,3-dioxan-2-ona (MCP). Los andamios poliméricos fueron bioconjugados con un número controlado de moléculas de 1,2-distearoil-sn-glicero-3-fosfoetanolamina (DSPE), ácido oleico o colesterol. La constatación de las estructuras se realizó empleando técnicas espectroscópicas de FT-IR y 1H-RMN. Sus distribuciones de peso molecular fueron obtenidas mediante cromatografía de permeación en gel (GPC). Las metodologías sintéticas propuestas resultaron ser viables para la obtención de materiales con pesos moleculares controlados y dispersiones estrechas, propiciando un control sobre la arquitectura de los copolímeros. Se evaluó la influencia de estas modificaciones estructurales en las propiedades morfológicas de los materiales empleando calorimetría diferencial de barrido (DSC). El estudio térmico de los copolímeros evidenció una disminución de la cristalinidad de los materiales bioconjugados y se determinó que la adición de estas biomoléculas en las estructuras permite modular las propiedades fisicoquímicas de los mismos. Mediante un análisis de componentes principales (ACP) se determinó que las propiedades de los copolímeros relacionadas con su potencial aplicación en el encapsulamiento de fármacos dependen de la naturaleza del segmento hidrofóbico y el número de unidades de carbonatos en las estructuras. De igual forma, se determinó que hay una gran influencia en la naturaleza de las biomoléculas conjugadas en las características de los materiales. Empleando la metodología de nanoprecipitación se obtuvo dispersiones micelares cuyos diámetros nanométricos fueron evaluados mediante dispersión dinámica de luz (DLS). Las nanopartículas autoensambladas a partir de copolímeros bioconjugados con DSPE demostraron tener carga superficial negativa y esta fue determinada mediante la medición de su potencial ζ. Estos nanotrasportadores demostraron ser sistemas termodinámicamente estables, evidenciado por una disminución drástica en los valores de concentraciones micelares críticas (CMC) de los sistemas bioconjugados. Adicionalmente, estos sistemas demostraron ser cinéticamente estables ya que sus transiciones térmicas en las cuales se evidenció una disminución de la cristalinidad de los copolímeros asociado a la presencia de grupos hidrofóbicos y voluminosos cuyas interacciones entre cadenas dificultan la formación de arreglos regulares obteniendo sistemas con un mayor volumen libre entre cadenas poliméricas en cuyos espacios se favorece el encapsulamiento de fármacos de baja hidrosolubilidad. Los copolímeros biomiméticos sintetizados en este trabajo de investigación corresponden a estructuras novedosas que aún no se encuentran reportadas en la literatura. Adicionalmente, los sistemas micelares obtenidos a partir del autoensamblaje de estos materiales en medio acuoso cumplen con los requerimientos para ser empleados en el transporte de fármacos y ofrecen perspectivas poderosas respecto del aumento de la magnitud sus interacciones de los copolímeros con la anfotericina B. |
| publishDate |
2020 |
| dc.date.accessioned.spa.fl_str_mv |
2020-08-05T07:36:26Z |
| dc.date.available.spa.fl_str_mv |
2020-08-05T07:36:26Z |
| dc.date.issued.spa.fl_str_mv |
2020-02-14 |
| dc.type.spa.fl_str_mv |
Documento de trabajo |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/workingPaper |
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info:eu-repo/semantics/acceptedVersion |
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http://purl.org/coar/resource_type/c_8042 |
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Text |
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http://purl.org/redcol/resource_type/WP |
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http://purl.org/coar/resource_type/c_8042 |
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acceptedVersion |
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Angarita Villamizar, A.V.E (2020) "Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos". Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia. |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/77929 |
| identifier_str_mv |
Angarita Villamizar, A.V.E (2020) "Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos". Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia. |
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https://repositorio.unal.edu.co/handle/unal/77929 |
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spa |
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spa |
| dc.relation.references.spa.fl_str_mv |
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Atribución-NoComercial-SinDerivadas 4.0 InternacionalDerechos reservados - Universidad Nacional de ColombiaAcceso abiertohttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Pérez Pérez, León Darío26c85caa-172a-4f24-8364-71a25423a2a9-1Angarita Villamizar, Angie Vivian Esther6b2a457c-64db-45a1-bf64-888785e66fe7Universidad Nacional de ColombiaGrupo de Investigación en Macromoléculas2020-08-05T07:36:26Z2020-08-05T07:36:26Z2020-02-14Angarita Villamizar, A.V.E (2020) "Síntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacos". Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia.https://repositorio.unal.edu.co/handle/unal/77929En el presente trabajo de investigación se sintetizó una biblioteca de materiales basados en copolímeros en bloque anfifílicos de composiciones variables empleando monómeros biocompatibles y altamente biodegradables de ε-caprolactona (ε-CL) y 5-metil-5-propargiloxicarbonil-1,3-dioxan-2-ona (MCP). Los andamios poliméricos fueron bioconjugados con un número controlado de moléculas de 1,2-distearoil-sn-glicero-3-fosfoetanolamina (DSPE), ácido oleico o colesterol. La constatación de las estructuras se realizó empleando técnicas espectroscópicas de FT-IR y 1H-RMN. Sus distribuciones de peso molecular fueron obtenidas mediante cromatografía de permeación en gel (GPC). Las metodologías sintéticas propuestas resultaron ser viables para la obtención de materiales con pesos moleculares controlados y dispersiones estrechas, propiciando un control sobre la arquitectura de los copolímeros. Se evaluó la influencia de estas modificaciones estructurales en las propiedades morfológicas de los materiales empleando calorimetría diferencial de barrido (DSC). El estudio térmico de los copolímeros evidenció una disminución de la cristalinidad de los materiales bioconjugados y se determinó que la adición de estas biomoléculas en las estructuras permite modular las propiedades fisicoquímicas de los mismos. Mediante un análisis de componentes principales (ACP) se determinó que las propiedades de los copolímeros relacionadas con su potencial aplicación en el encapsulamiento de fármacos dependen de la naturaleza del segmento hidrofóbico y el número de unidades de carbonatos en las estructuras. De igual forma, se determinó que hay una gran influencia en la naturaleza de las biomoléculas conjugadas en las características de los materiales. Empleando la metodología de nanoprecipitación se obtuvo dispersiones micelares cuyos diámetros nanométricos fueron evaluados mediante dispersión dinámica de luz (DLS). Las nanopartículas autoensambladas a partir de copolímeros bioconjugados con DSPE demostraron tener carga superficial negativa y esta fue determinada mediante la medición de su potencial ζ. Estos nanotrasportadores demostraron ser sistemas termodinámicamente estables, evidenciado por una disminución drástica en los valores de concentraciones micelares críticas (CMC) de los sistemas bioconjugados. Adicionalmente, estos sistemas demostraron ser cinéticamente estables ya que sus transiciones térmicas en las cuales se evidenció una disminución de la cristalinidad de los copolímeros asociado a la presencia de grupos hidrofóbicos y voluminosos cuyas interacciones entre cadenas dificultan la formación de arreglos regulares obteniendo sistemas con un mayor volumen libre entre cadenas poliméricas en cuyos espacios se favorece el encapsulamiento de fármacos de baja hidrosolubilidad. Los copolímeros biomiméticos sintetizados en este trabajo de investigación corresponden a estructuras novedosas que aún no se encuentran reportadas en la literatura. Adicionalmente, los sistemas micelares obtenidos a partir del autoensamblaje de estos materiales en medio acuoso cumplen con los requerimientos para ser empleados en el transporte de fármacos y ofrecen perspectivas poderosas respecto del aumento de la magnitud sus interacciones de los copolímeros con la anfotericina B.In the present research a library of materials based on amphiphilic block copolymers of variable compositions was synthesized using biocompatible and highly biodegradable monomers of ε-caprolactone (ε-CL) and 5-methyl-5-propargiloxycarbonyl-1,3-dioxan -2-one (MCP). The polymeric scaffolds were bioconjugated with a controlled number of 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine (DSPE), oleic acid, or cholesterol molecules. The verification of the structures was carried out using FT-IR and 1H-NMR spectroscopic techniques. Their molecular weight distributions were obtained by gel permeation chromatography (GPC). The proposed synthetic methodologies turned out to be viable for obtaining materials with controlled molecular weights and narrow dispersions, promoting control over the architecture of the copolymers. The influence of these structural modifications on the morphological properties of the materials was evaluated using differential scanning calorimetry (DSC). The thermal study of the copolymers showed a decrease in the crystallinity of the bioconjugated materials and it was determined that the addition of these biomolecules in the structures allows modulating their physicochemical properties. By means of a principal component analysis (PCA) it was determined that the properties of the copolymers related to their potential application in the encapsulation of drugs depend on the nature of the hydrophobic segment and the number of carbonate units in the structures. Similarly, it was determined that there is a great influence on the nature of conjugated biomolecules on the characteristics of the materials. Using the nanoprecipitation methodology, micellar dispersions were obtained whose nanometric diameters were evaluated by dynamic light scattering (DLS). Self-assembled nanoparticles from bioconjugated copolymers with DSPE were shown to have a negative surface charge and this was determined by measuring their potential ζ. These nano transporters proved to be thermodynamically stable systems, evidenced by a drastic decrease in the critical micellar concentration (CMC) values of the bioconjugated systems. Additionally, these systems proved to be kinetically stable since their thermal transitions in which a decrease in the crystallinity of the copolymers was evidenced, associated with the presence of hydrophobic and bulky groups whose interactions between chains hinder the formation of regular arrangements obtaining systems with a higher free volume between polymer chains in whose spaces the encapsulation of drugs of low water solubility is favored. The biomimetic copolymers synthesized in this research work correspond to novel structures that have not yet been reported in the literature. Additionally, the micellar systems obtained from the self-assembly of these materials in an aqueous medium meet the requirements to be used in the transport of drugs and offer powerful perspectives regarding the magnitude increase in their interactions of the copolymers with amphotericin B.COLCIENCIAS"Diseño de formulaciones orales de Anfotericina B encapsulada en nanopartículas poliméricas biodegradables y su eficacia frente a levaduras multi-drogo resistentes: Una aproximación a partir de las interacciones fármaco – polímero”Línea de Investigación: Síntesis de Polímeros.Maestría201application/pdfspa540 - Química y ciencias afines660 - Ingeniería químicaAnfotericina BcopolímerospolicaprolactonabiomoléculasmicelasAmphotericin BcopolymerspolycaprolactonebiomoleculesmicellesSíntesis de copolímeros dibloque biodegradables conjugados con biomoléculas como plataforma de administración de fármacosDocumento de trabajoinfo:eu-repo/semantics/workingPaperinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_8042Texthttp://purl.org/redcol/resource_type/WPBogotá - Ciencias - Maestría en Ciencias - QuímicaDepartamento de QuímicaUniversidad Nacional de Colombia - Sede BogotáAdams, M. 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(2016) ‘Thermodynamics and kinetics of amphotericin B self-association in aqueous solution characterized in molecular detail’, Scientific Reports, 6. doi: 10.1038/srep19109.ORIGINAL1015413321.2020.pdf.pdf1015413321.2020.pdf.pdfapplication/pdf9818944https://repositorio.unal.edu.co/bitstream/unal/77929/1/1015413321.2020.pdf.pdf7b0f48341621120be20f762ea80f9763MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.unal.edu.co/bitstream/unal/77929/3/license_rdf217700a34da79ed616c2feb68d4c5e06MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-83991https://repositorio.unal.edu.co/bitstream/unal/77929/2/license.txt6f3f13b02594d02ad110b3ad534cd5dfMD52THUMBNAIL1015413321.2020.pdf.pdf.jpg1015413321.2020.pdf.pdf.jpgGenerated Thumbnailimage/jpeg5573https://repositorio.unal.edu.co/bitstream/unal/77929/4/1015413321.2020.pdf.pdf.jpg849170b87a94d920eabedcfbb72cabcaMD54unal/77929oai:repositorio.unal.edu.co:unal/779292023-07-11 23:03:31.434Repositorio 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