Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems

The copper(I)-catalyzed azide/alkyne cycloaddition is recognized as one of the most successful click reactions to access self-assembling amphiphilic polymer-drug conjugates (PDCs). In this way, poor water-soluble drugs can be linked covalently to hydrophilic poly(ethylene glycol) (PEG) to obtain PEG...

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Autores: López Quijorna, Sonia, Rodríguez López, Julián, García González, María Teresa, Rodríguez Romero, Juan Francisco, Pérez-Ortiz, José M., Ramos Marcos, María Jesús, Gracia Fernández, Ignacio
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/30260
Acceso en línea:http://hdl.handle.net/10578/30260
Access Level:acceso abierto
Palabra clave:Anticancer
Polymer-drug conjugates
Drug delivery
Micelles
Click chemistry
Contra el cáncer
Conjugados polímero-fármaco
Entrega de medicamentos
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
title Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
spellingShingle Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
López Quijorna, Sonia
Anticancer
Polymer-drug conjugates
Drug delivery
Micelles
Click chemistry
Contra el cáncer
Conjugados polímero-fármaco
Entrega de medicamentos
title_short Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
title_full Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
title_fullStr Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
title_full_unstemmed Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
title_sort Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systems
dc.creator.none.fl_str_mv López Quijorna, Sonia
Rodríguez López, Julián
García González, María Teresa
Rodríguez Romero, Juan Francisco
Pérez-Ortiz, José M.
Ramos Marcos, María Jesús
Gracia Fernández, Ignacio
author López Quijorna, Sonia
author_facet López Quijorna, Sonia
Rodríguez López, Julián
García González, María Teresa
Rodríguez Romero, Juan Francisco
Pérez-Ortiz, José M.
Ramos Marcos, María Jesús
Gracia Fernández, Ignacio
author_role author
author2 Rodríguez López, Julián
García González, María Teresa
Rodríguez Romero, Juan Francisco
Pérez-Ortiz, José M.
Ramos Marcos, María Jesús
Gracia Fernández, Ignacio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Anticancer
Polymer-drug conjugates
Drug delivery
Micelles
Click chemistry
Contra el cáncer
Conjugados polímero-fármaco
Entrega de medicamentos
topic Anticancer
Polymer-drug conjugates
Drug delivery
Micelles
Click chemistry
Contra el cáncer
Conjugados polímero-fármaco
Entrega de medicamentos
description The copper(I)-catalyzed azide/alkyne cycloaddition is recognized as one of the most successful click reactions to access self-assembling amphiphilic polymer-drug conjugates (PDCs). In this way, poor water-soluble drugs can be linked covalently to hydrophilic poly(ethylene glycol) (PEG) to obtain PEGylated drug micelles that can be used as versatile carriers for the delivery of diverse therapeutic agents. In this work, two novel amphiphilic PDCs that combine PEG with privileged scaffolds well-known for their anticancer properties, such as coumarin and 5-fluorouracil, have been synthesized and characterized. These conjugates were able to self-assemble into micelles at relatively high critical micellar concentration, probably due to the large portion of hydrophilic PEG. The micelles allowed to load other anticancer drugs (paclitaxel, curcumin, and gemcitabine), providing a unique opportunity to develop promising co-delivery carriers for synergistic cancer therapy. The Korsmeyer-Peppas mathematical model was used for describing the in vitro kinetics of drug release from the micelles. Similar sustained and controlled drug release profiles were obtained for paclitaxel and curcumin in both conjugates, which was attributed to the excellent stability driven by the strong interaction between polymeric conjugates and drugs in the micelle core. In contrast, the high instability observed for the gemcitabine-loaded micelles provided an initial uncontrolled burst release of drug. A preliminary in vitro cytotoxicity study of the micelles against human pancreatic cancer cells PANC-1 and BxPC-3 was also carried out, demonstrating that both coumarin and 5-fluorouracil retain their anticancer properties after conjugation with PEG.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10578/30260
url http://hdl.handle.net/10578/30260
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Self-assembled coumarin- and 5-fluorouracil-PEG micelles as multifunctional drug delivery systemsLópez Quijorna, SoniaRodríguez López, JuliánGarcía González, María TeresaRodríguez Romero, Juan FranciscoPérez-Ortiz, José M.Ramos Marcos, María JesúsGracia Fernández, IgnacioAnticancerPolymer-drug conjugatesDrug deliveryMicellesClick chemistryContra el cáncerConjugados polímero-fármacoEntrega de medicamentosThe copper(I)-catalyzed azide/alkyne cycloaddition is recognized as one of the most successful click reactions to access self-assembling amphiphilic polymer-drug conjugates (PDCs). In this way, poor water-soluble drugs can be linked covalently to hydrophilic poly(ethylene glycol) (PEG) to obtain PEGylated drug micelles that can be used as versatile carriers for the delivery of diverse therapeutic agents. In this work, two novel amphiphilic PDCs that combine PEG with privileged scaffolds well-known for their anticancer properties, such as coumarin and 5-fluorouracil, have been synthesized and characterized. These conjugates were able to self-assemble into micelles at relatively high critical micellar concentration, probably due to the large portion of hydrophilic PEG. The micelles allowed to load other anticancer drugs (paclitaxel, curcumin, and gemcitabine), providing a unique opportunity to develop promising co-delivery carriers for synergistic cancer therapy. The Korsmeyer-Peppas mathematical model was used for describing the in vitro kinetics of drug release from the micelles. Similar sustained and controlled drug release profiles were obtained for paclitaxel and curcumin in both conjugates, which was attributed to the excellent stability driven by the strong interaction between polymeric conjugates and drugs in the micelle core. In contrast, the high instability observed for the gemcitabine-loaded micelles provided an initial uncontrolled burst release of drug. A preliminary in vitro cytotoxicity study of the micelles against human pancreatic cancer cells PANC-1 and BxPC-3 was also carried out, demonstrating that both coumarin and 5-fluorouracil retain their anticancer properties after conjugation with PEG.La cicloadición de azida/alquino catalizada por cobre (I) se reconoce como una de las reacciones de clic más exitosas para acceder a conjugados de polímero-fármaco anfifílicos (PDC) autoensamblados. De esta manera, los fármacos poco solubles en agua se pueden unir covalentemente al poli(etilenglicol) (PEG) hidrofílico para obtener micelas de fármacos PEGilados que se pueden utilizar como vehículos versátiles para la administración de diversos agentes terapéuticos. En este trabajo, dos PDC anfifílicos novedosos que combinan PEG con andamios privilegiados conocidos por sus propiedades anticancerígenas, como la cumarina .y 5-fluorouracilo, han sido sintetizados y caracterizados. Estos conjugados pudieron autoensamblarse en micelas a una concentración micelar crítica relativamente alta, probablemente debido a la gran porción de PEG hidrofílico. Las micelas permitieron cargar otros medicamentos contra el cáncer (paclitaxel, curcumina y gemcitabina), lo que brinda una oportunidad única para desarrollar portadores de administración conjunta prometedores para la terapia sinérgica contra el cáncer. Se utilizó el modelo matemático de Korsmeyer-Peppas para describir la cinética in vitro de la liberación del fármaco desde las micelas. Se obtuvieron perfiles similares de liberación sostenida y controlada del fármaco para paclitaxel.y curcumina en ambos conjugados, lo que se atribuyó a la excelente estabilidad impulsada por la fuerte interacción entre los conjugados poliméricos y los fármacos en el núcleo de la micela. Por el contrario, la alta inestabilidad observada para las micelas cargadas con gemcitabina proporcionó una liberación inicial descontrolada del fármaco. También se llevó a cabo un estudio preliminar de citotoxicidad in vitro de las micelas contra las células de cáncer de páncreas humano PANC-1 y BxPC-3, demostrando que tanto la cumarina como el 5-fluorouracilo conservan sus propiedades anticancerígenas después de la conjugación con PEG.Elsevier202220222022info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10578/30260reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/302602026-05-27T07:36:41Z
score 15,301603

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