Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery

[eng] This thesis, entitled "Multifunctional Self-stratified Polyurethane-Polyurea Nanosystems for Smart Drug Delivery" is structured as a compendium of publications, being organized around a methodological synthetic patent and four internationally peer reviewed publications on the chemica...

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Detalles Bibliográficos
Autor: Rocas Alonso, Pau
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/102994
Acceso en línea:https://hdl.handle.net/2445/102994
http://hdl.handle.net/10803/396322
Access Level:acceso abierto
Palabra clave:Nanopartícules
Nanotecnologia
Poliuretans
Càncer
Medicaments
Nanoparticles
Nanotechnology
Polyurethanes
Cancer
Drugs
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oai_identifier_str oai:diposit.ub.edu:2445/102994
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
title Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
spellingShingle Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
Rocas Alonso, Pau
Nanopartícules
Nanotecnologia
Poliuretans
Càncer
Medicaments
Nanoparticles
Nanotechnology
Polyurethanes
Cancer
Drugs
title_short Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
title_full Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
title_fullStr Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
title_full_unstemmed Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
title_sort Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug delivery
dc.creator.none.fl_str_mv Rocas Alonso, Pau
author Rocas Alonso, Pau
author_facet Rocas Alonso, Pau
author_role author
dc.contributor.none.fl_str_mv Albericio Palomera, Fernando
Universitat de Barcelona. Departament de Química Orgànica
dc.subject.none.fl_str_mv Nanopartícules
Nanotecnologia
Poliuretans
Càncer
Medicaments
Nanoparticles
Nanotechnology
Polyurethanes
Cancer
Drugs
topic Nanopartícules
Nanotecnologia
Poliuretans
Càncer
Medicaments
Nanoparticles
Nanotechnology
Polyurethanes
Cancer
Drugs
description [eng] This thesis, entitled "Multifunctional Self-stratified Polyurethane-Polyurea Nanosystems for Smart Drug Delivery" is structured as a compendium of publications, being organized around a methodological synthetic patent and four internationally peer reviewed publications on the chemical and bio-applicability of the US and EU patented invention. Thus, this manuscript is divided into a General Introduction to drug delivery with polyurethane-polyurea nanosystems and three chapters, which include the publications as Results and Discussion and their introductions as Introduction of each chapter. Chapter 1 is focused on the synthetic methodology to produce a novel kind of self-stratified multifunctional polyurethane-polyurea nanoparticles for cancer nanotherapy. The Introduction of this chapter deals with the key characteristics of drug delivery nanosystems and presents the basis of self-stratification by hydrophobic effects. This chapter contains a methodological patent that breaks down multiple examples of nanoparticles formed by easy-tunable polyurethane-polyurea biocompatible and biodegradable polymers bearing multifunctionalities that are applied to cancer therapy and imaging. In addition, here we include a publication containing the in vitro proof-of-principle of the stratified nature, high encapsulation stability and selective targeting to cancer cells of the nanosystem. Finally, this chapter also contains a publication with the in vivo proof-of-concept for avf33 integrin targeted cancer therapy and imaging of polyurethane-polyurea nanoparticles encapsulating plitidepsin as antiangiogenic drug. This research is the consequence of a fruitful collaboration in the framework of a INNPACTO national project (Polysfera, IPT-090000-2010-1) with Dr. P. Calvo, Dr. P. Aviles and Dr. M. J. Guinan in PharmaMar SA; Dr. I. Abasolo, Dr. Y. Fernandez and Dr. S. Schwartz in Vail d'Hebron Institut de Recerca and Dr. J. Rocas in Ecopol Tech SL. Chapter 2 arises from the encouraging results obtained from Chapter 1 in novel synthetic methods of polymer nanoparticles with shell stratification capacity. The Introduction of this chapter presents the current concerns with titanium implants, the outcome of nanoparticle-coated biomaterials and the perspectives in multifunctional nanomaterials. In this regard, a fantastic collaboration with Dr. C. Mas-Moruno of the BiBiTE group in the UPC lead taking profit of the cell targeting high specificity and great encapsulation capacity of PUUa NPs to develop new generation nanobiomaterials for the enhancement of titanium implants osseointegration and bacterial infection prevention. Titanium implants were innovatively coated by interfacial functionalization with RGD-decorated and roxithromycin-loaded PUUa NPs. This methodology resulted in an outstanding improvement of osteoblastic cells adhesion as well as a dramatic reduction of S. Sanguinis bacteria adhesion onto titanium, which is of great interest to improve the outcome of metallic implants for regenerative medicine. In Chapter 3, we explore another segment of application of PUUa NPs, this is immunotherapy. In collaboration with G. Florez-Canals, Dr. D. Benitez-Ribas and Dr. J. Panes in IDIBAPS and Hospital Clínic of Barcelona we applied PUUa NPs encapsulating budesonide (BDS) corticosteroid for the improvement of BDS efficacy to induce tolerogenicity to dendritic cells (DCs). The Introduction deals with the current therapies used to treat autoimmune diseases as well as recent strategies to target dendritic cells in vivo using smart nanoparticles encapsulating immunosuppressive drugs. Herein we found that when PUUa NPs loaded with BDS were incubated with mature DCs, those differentiated into tolerogenic dendritic cells in a much more efficient manner than DCs incubated with free BDS. As shown in the included publication, levels of costimulatory molecules were enhanced and IL-10 immunosuppressive cytokine was largely secreted. Even more interestingly, fluorescently labeled PUUa NPs proved their DCs targeted behavior in a multi-cellular environment.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/102994
http://hdl.handle.net/10803/396322
url https://hdl.handle.net/2445/102994
http://hdl.handle.net/10803/396322
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Rocas, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Rocas, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Química Orgànica
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Multifunctional self-stratified polyurethane-polyurea nanosystems for smart drug deliveryRocas Alonso, PauNanopartículesNanotecnologiaPoliuretansCàncerMedicamentsNanoparticlesNanotechnologyPolyurethanesCancerDrugs[eng] This thesis, entitled "Multifunctional Self-stratified Polyurethane-Polyurea Nanosystems for Smart Drug Delivery" is structured as a compendium of publications, being organized around a methodological synthetic patent and four internationally peer reviewed publications on the chemical and bio-applicability of the US and EU patented invention. Thus, this manuscript is divided into a General Introduction to drug delivery with polyurethane-polyurea nanosystems and three chapters, which include the publications as Results and Discussion and their introductions as Introduction of each chapter. Chapter 1 is focused on the synthetic methodology to produce a novel kind of self-stratified multifunctional polyurethane-polyurea nanoparticles for cancer nanotherapy. The Introduction of this chapter deals with the key characteristics of drug delivery nanosystems and presents the basis of self-stratification by hydrophobic effects. This chapter contains a methodological patent that breaks down multiple examples of nanoparticles formed by easy-tunable polyurethane-polyurea biocompatible and biodegradable polymers bearing multifunctionalities that are applied to cancer therapy and imaging. In addition, here we include a publication containing the in vitro proof-of-principle of the stratified nature, high encapsulation stability and selective targeting to cancer cells of the nanosystem. Finally, this chapter also contains a publication with the in vivo proof-of-concept for avf33 integrin targeted cancer therapy and imaging of polyurethane-polyurea nanoparticles encapsulating plitidepsin as antiangiogenic drug. This research is the consequence of a fruitful collaboration in the framework of a INNPACTO national project (Polysfera, IPT-090000-2010-1) with Dr. P. Calvo, Dr. P. Aviles and Dr. M. J. Guinan in PharmaMar SA; Dr. I. Abasolo, Dr. Y. Fernandez and Dr. S. Schwartz in Vail d'Hebron Institut de Recerca and Dr. J. Rocas in Ecopol Tech SL. Chapter 2 arises from the encouraging results obtained from Chapter 1 in novel synthetic methods of polymer nanoparticles with shell stratification capacity. The Introduction of this chapter presents the current concerns with titanium implants, the outcome of nanoparticle-coated biomaterials and the perspectives in multifunctional nanomaterials. In this regard, a fantastic collaboration with Dr. C. Mas-Moruno of the BiBiTE group in the UPC lead taking profit of the cell targeting high specificity and great encapsulation capacity of PUUa NPs to develop new generation nanobiomaterials for the enhancement of titanium implants osseointegration and bacterial infection prevention. Titanium implants were innovatively coated by interfacial functionalization with RGD-decorated and roxithromycin-loaded PUUa NPs. This methodology resulted in an outstanding improvement of osteoblastic cells adhesion as well as a dramatic reduction of S. Sanguinis bacteria adhesion onto titanium, which is of great interest to improve the outcome of metallic implants for regenerative medicine. In Chapter 3, we explore another segment of application of PUUa NPs, this is immunotherapy. In collaboration with G. Florez-Canals, Dr. D. Benitez-Ribas and Dr. J. Panes in IDIBAPS and Hospital Clínic of Barcelona we applied PUUa NPs encapsulating budesonide (BDS) corticosteroid for the improvement of BDS efficacy to induce tolerogenicity to dendritic cells (DCs). The Introduction deals with the current therapies used to treat autoimmune diseases as well as recent strategies to target dendritic cells in vivo using smart nanoparticles encapsulating immunosuppressive drugs. Herein we found that when PUUa NPs loaded with BDS were incubated with mature DCs, those differentiated into tolerogenic dendritic cells in a much more efficient manner than DCs incubated with free BDS. As shown in the included publication, levels of costimulatory molecules were enhanced and IL-10 immunosuppressive cytokine was largely secreted. Even more interestingly, fluorescently labeled PUUa NPs proved their DCs targeted behavior in a multi-cellular environment.[spa] Esta tesis, titulada "Multifunctional Self-stratified Polyurethane-polyurea Nanosystems for Smart Drug Delivery" está estructurada como un compendio de cuatro publicaciones en revistas internacionales sobre la química y bio-aplicabilidad de nuestra técnica organizadas alrededor de una patente sintética y metodológica de la invención. El capítulo 1 se centra en la metodología sintética para producir un nuevo tipo de nanopartículas multifuncionales autoestratificadas de Poliuretano-poliurea para la terapia del cáncer. Este capítulo contiene una patente metodológica que analiza múltiples ejemplos de nanopartículas versátiles de Poliuretano-poliurea biocompatibles y biodegradables para el tratamiento del cáncer. Además, aquí se incluye una publicación que contiene la demostración de la estratificación de las nanopartículas, la alta estabilidad de encapsulación y la internalización selectiva in vitro de las nanopartículas en células cancerosas U87-MG. Por último, este capítulo también contiene una publicación con la prueba de concepto in vivo de la menor toxicidad, mejor biodistribución y farmacocinética en plasma sanguíneo de las nanopartículas de Poliuretano-poliurea encapsulando plitidepsina como fármaco antiangiogénico comparado con el fármaco libre. El capítulo 2 surge de los buenos resultados obtenidos del capítulo 1 en nuevos métodos de síntesis de nanopartículas poliméricas con capacidad de autoestratificación. Aquí se investigan nanobiomateriales de nueva generación recubiertos de nanopartículas de poliuretano y poliurea para mejorar la osteointegración y prevenir la infección bacteriana de implantes de titanio. Así pues, implantes de titanio fueron recubiertos superficialmente con PUUa NPs con péptido RGD en la membrana y cargadas de roxitromicina en su interior. Esta metodología dio lugar a una mejora excepcional en la adhesión de células osteoblásticas así como una reducción dramática de la adhesión bacterias S. Sanguinis en titanio, que resulta de gran interés para mejorar la vida útil de los implantes metálicos para medicina regenerativa. En el capítulo 3, exploramos otro segmento de aplicación de las nanopartículas de poliuretano y poliurea, esta es la inmunoterapia. Se aplicaron nanopartículas cargadas con el corticosteroide budesonida para su mejora como fármaco inmunosupresor para la terapia con células dendríticas. Aqui demostramos que la budesonida encapsulada es mucho más efectiva que la libre en células dendríticas humanas.Universitat de BarcelonaAlbericio Palomera, FernandoUniversitat de Barcelona. Departament de Química Orgànica2016info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/102994http://hdl.handle.net/10803/396322Tesis Doctorals - Departament - Química Orgànicareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Rocas, 2016info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1029942026-05-27T06:46:51Z
score 15,300719

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