Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana

ilustraciones, gráficas, tablas

Autores:: Cardona Paredes, María Isabel

Tipo de recurso:: Doctoral thesis

Fecha de publicación:: 2022

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
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repository_id_str
dc.title.none.fl_str_mv	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
dc.title.translated.eng.fl_str_mv	Development of muco-penetrating systems for oral administration as a strategy to increase the bioavailability of the flavonoid rutin of an extract of calyces from Physalis peruviana
title	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
spellingShingle	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana 610 - Medicina y salud::615 - Farmacología y terapéutica 540 - Química y ciencias afines::547 - Química orgánica 540 - Química y ciencias afines Plantas medicinales Plantas útiles Medicinal plant Plants, useful Physalis peruviana Rutina Extracto vegetal Sistema autoemulsificable Micropartículas Mucopenetración Biodisponibilidad Physalis peruviana Rutin Herbal extract Self-emulsifying drug delivery systems, Microparticles Mucopenetration Bioavailability
title_short	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
title_full	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
title_fullStr	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
title_full_unstemmed	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
title_sort	Desarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruviana
dc.creator.fl_str_mv	Cardona Paredes, María Isabel
dc.contributor.advisor.none.fl_str_mv	Aragón Novoa, Diana Marcela Bernkop-Schnürch, Andreas
dc.contributor.author.none.fl_str_mv	Cardona Paredes, María Isabel
dc.contributor.researchgroup.spa.fl_str_mv	Tecnología de productos naturales
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::615 - Farmacología y terapéutica 540 - Química y ciencias afines::547 - Química orgánica 540 - Química y ciencias afines
topic	610 - Medicina y salud::615 - Farmacología y terapéutica 540 - Química y ciencias afines::547 - Química orgánica 540 - Química y ciencias afines Plantas medicinales Plantas útiles Medicinal plant Plants, useful Physalis peruviana Rutina Extracto vegetal Sistema autoemulsificable Micropartículas Mucopenetración Biodisponibilidad Physalis peruviana Rutin Herbal extract Self-emulsifying drug delivery systems, Microparticles Mucopenetration Bioavailability
dc.subject.lemb.spa.fl_str_mv	Plantas medicinales Plantas útiles
dc.subject.lemb.eng.fl_str_mv	Medicinal plant Plants, useful
dc.subject.proposal.spa.fl_str_mv	Physalis peruviana Rutina Extracto vegetal Sistema autoemulsificable Micropartículas Mucopenetración Biodisponibilidad
dc.subject.proposal.eng.fl_str_mv	Physalis peruviana Rutin Herbal extract Self-emulsifying drug delivery systems, Microparticles Mucopenetration Bioavailability
description	ilustraciones, gráficas, tablas
publishDate	2022
dc.date.accessioned.none.fl_str_mv	2022-09-01T14:09:37Z
dc.date.available.none.fl_str_mv	2022-09-01T14:09:37Z
dc.date.issued.none.fl_str_mv	2022
dc.type.spa.fl_str_mv	Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv	http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TD
format	http://purl.org/coar/resource_type/c_db06
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/82232
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/82232 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
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dc.rights.license.spa.fl_str_mv	Atribución-NoComercial-SinDerivadas 4.0 Internacional
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rights_invalid_str_mv	Atribución-NoComercial-SinDerivadas 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_abf2
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dc.format.extent.spa.fl_str_mv	xxv, 230 páginas
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Bogotá - Ciencias - Doctorado en Ciencias Farmacéuticas
dc.publisher.department.spa.fl_str_mv	Departamento de Farmacia
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
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repository.name.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
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spelling	Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Aragón Novoa, Diana Marcelae90c0e226a8f429821e3c3ec5b3f5ed1Bernkop-Schnürch, Andreas5b7e2b6d6106641120a9d39955852689Cardona Paredes, María Isabel311432a14c62d5c7f847271ad5b97459Tecnología de productos naturales2022-09-01T14:09:37Z2022-09-01T14:09:37Z2022https://repositorio.unal.edu.co/handle/unal/82232Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficas, tablasPhysalis peruviana L., es una planta ampliamente cultivada en los Andes sudamericanos con propiedades medicinales. Sus cálices son utilizados en la medicina tradicional por sus propiedades como anticancerígeno, antimicrobiano, antipirético, diurético y antiinflamatorio. Rutina, el flavonoide mayoritario del extracto etanólico de cálices de P. peruviana se ha utilizado en el tratamiento de diversas enfermedades. Sin embargo, la mayor limitación asociada a rutina es su baja biodisponibilidad oral, causada principalmente por su inestabilidad, baja solubilidad acuosa y limitada mucopenetración. El objetivo de esta investigación fue desarrollar dos sistemas mucopenetrantes (sistema autoemulsificable y micropartículas poliméricas) con el fin de incrementar la biodisponibilidad oral de la rutina presente en un extracto de cálices de P. peruviana. Inicialmente y como parte de la pre-formulación de los sistemas, se llevó a cabo la caracterización del extracto de cálices de P. peruviana y el estudio de estabilidad bajo condiciones de estrés y almacenamiento. Posteriormente, se desarrolló un sistema autoemulsificable cargado con el éster láurico de rutina aplicando una estrategia novedosa para incrementar la mucopenetración del mismo. Con dicha información como punto de partida, se desarrollaron y optimizaron dos sistemas mucopenetrantes (sistema autoemulsificable y micropartículas poliméricas) cargados con el extracto de cálices de P. peruviana a los cuáles se les evaluó la mucopenetración utilizando el método Transwell y su efecto sobre las propiedades reológicas del mucus intestinal porcino con el fin de entender los factores involucrados en la mucopenetración. Posteriormente, se determinó la farmacocinética y biodisponibilidad oral de rutina tras la administración del sistema autoemulsificable desarrollado y se comparó con el extracto no formulado. Finalmente, se evaluó la actividad hipoglicemiante del extracto no formulado y del sistema autoemulsificable por medio de un modelo in vivo de tolerancia a la glucosa en ratones. De acuerdo con los resultados obtenidos, se logró incorporar el extracto de cálices de P. peruviana en dos sistemas mucopenetrantes (sistema autoemulsificable y micropartículas poliméricas). La estrategia para incrementar la mucopenetración de las micropartículas se realizó utilizando Pluronic F127 mientras que para el sistema autoemulsificable fue la incorporación del copolímero PDMSHEPMS en la formulación. Se observó que el sistema autoemulsificable es más promisorio para el extracto de cálices de P. peruviana ya que permitió obtener una mayor mucopenetración, además su preparación es más simple y rentable con respecto a las micropartículas. La incorporación de PDMSHEPMS en el sistema autoemulsificable incrementó la mucopenetración de rutina 1,9 veces, siendo una estrategia novedosa y sencilla para favorecer la mucopenetración de este tipo de sistemas. En cuanto al estudio de biodisponibilidad, se observó un aumento de 5,81 veces en la biodisponibilidad oral de quercetina (principal metabolito de rutina en plasma), así como un aumento en la velocidad de absorción tras la administración oral del sistema autoemulsificable desarrollado con respecto al extracto no formulado. Adicionalmente, la reducción de los niveles de glucosa en sangre de los animales tratados con el sistema autoemulsificable fue similar a la producida por el fármaco glibenclamida lo cual es muy prometedor para un sistema de administración cargado con un extracto vegetal completo. (Texto tomado de la fuente)Physalis peruviana L. is a plant widely cultivated in the South American Andes with medicinal properties. The calyces of P. peruviana are used in folk medicine for their properties as anticancer, antimicrobial, antipyretic, diuretic, and anti¬inflammatory. Rutin is the major flavonoid in P. peruviana calyces extract, this flavonoid has been used in the treatment of different diseases. However, the major limitation associated with rutin is its poor bioavailability, mainly caused by its poor stability, low aqueous solubility, and limited mucopenetration. The aim of this research was to develop two mucus-penetrating systems (self-emulsifying drug delivery system and polymeric microparticles) to increase the oral bioavailability of rutin of an extract of calyces from P. peruviana. Initially and as part of the pre-formulation, the characterization of the extract and the stability study under stress and storage conditions were carried out. Subsequently, a rutin ester-loaded self-emulsifying drug delivery system was developed using a novel strategy to enhance its mucus permeation. With this information, two mucus-penetrating systems loaded with the extract of calyces from P. peruviana were developed and optimized (self-emulsifying drug delivery system and polymeric microparticles). The mucopenetration of the systems was evaluated using the Transwell method and its effect on the rheology properties of porcine intestinal mucus was also evaluated in order to understand the factors associated with mucopenetration. Subsequently, pharmacokinetics and oral bioavailability of rutin were evaluated after the administration of the developed self-emulsifying drug delivery system and it was compared with the unformulated extract. Finally, the hypoglycemic activity of the unformulated extract and of the self-emulsifying drug delivery system was evaluated with the in vivo model of glucose tolerance in mice. According to the results, it was possible to incorporate the extract of calyces from P. peruviana in two mucus-penetrating systems (self-emulsifying drug delivery system and polymeric microparticles). The strategy used to increase the mucus penetration of the microparticles was carried out using Pluronic F127 while for the self-emulsifying drug delivery system was the incorporation of the copolymer PDMSHEPMS in the formulation. According to the results obtained, the self-emulsifying drug delivery system is the most promising system for the extract of calyces from P. peruviana because exhibited higher mucus permeating properties compared to microparticles. In addition, the preparation of a self-emulsifying drug delivery system is simpler and more cost-efficient. The incorporation of PDMSHEPMS in the self-emulsifying drug delivery system increased the mucus permeation of rutin 1,9-fold, being a novel and simple strategy to enhance the mucus permeation of this type of system. Regarding the bioavailability study, the extract-loaded self-emulsifying drug delivery system showed a 5,81-fold increase in the oral bioavailability of quercetin, the main metabolite of rutin in plasma, as compared to the unformulated extract. Additionally, the reduction of blood glucose levels in animals treated with the optimized self-emulsifying drug delivery system was similar to those produced by glibenclamide, which is very promising for a drug delivery system loaded with a whole vegetal extract.DoctoradoDoctor en Ciencias FarmacéuticasTecnología farmacéuticaxxv, 230 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en Ciencias FarmacéuticasDepartamento de FarmaciaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéutica540 - Química y ciencias afines::547 - Química orgánica540 - Química y ciencias afinesPlantas medicinalesPlantas útilesMedicinal plantPlants, usefulPhysalis peruvianaRutinaExtracto vegetalSistema autoemulsificableMicropartículasMucopenetraciónBiodisponibilidadPhysalis peruvianaRutinHerbal extractSelf-emulsifying drug delivery systems,MicroparticlesMucopenetrationBioavailabilityDesarrollo de sistemas mucopenetrantes de administración oral como estrategia para aumentar la biodisponibilidad del flavonoide rutina en un extracto de cálices de Physalis peruvianaDevelopment of muco-penetrating systems for oral administration as a strategy to increase the bioavailability of the flavonoid rutin of an extract of calyces from Physalis peruvianaTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDAbdalla, A., Klein, S., & Mäder, K. 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Drug Development and Industrial Pharmacy, 43(10), 1694–1702.EstudiantesInvestigadoresMaestrosLICENSElicense.txtlicense.txttext/plain; charset=utf-84675https://repositorio.unal.edu.co/bitstream/unal/82232/3/license.txtb577153cc0e11f0aeb5fc5005dc82d8aMD53ORIGINAL1017126699. 2022.pdf1017126699. 2022.pdfTesis de Doctorado en Ciencias Farmacéuticasapplication/pdf4224984https://repositorio.unal.edu.co/bitstream/unal/82232/4/1017126699.%202022.pdfb0a8e8d1786061cbc331af351d655006MD54unal/82232oai:repositorio.unal.edu.co:unal/822322023-01-23 12:34:54.688Repositorio Institucional Universidad Nacional de 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