{"id":116447,"date":"2014-10-10T00:00:00","date_gmt":"2014-10-10T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/development-of-nanoparticles-encapsulating-bioactive-peptides-to-recover-telomerase-activity-application-in-the-treatment-of-dyskeratosis-congenita\/"},"modified":"2014-10-10T00:00:00","modified_gmt":"2014-10-10T00:00:00","slug":"development-of-nanoparticles-encapsulating-bioactive-peptides-to-recover-telomerase-activity-application-in-the-treatment-of-dyskeratosis-congenita","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/evaluacion-de-farmacos\/development-of-nanoparticles-encapsulating-bioactive-peptides-to-recover-telomerase-activity-application-in-the-treatment-of-dyskeratosis-congenita\/","title":{"rendered":"Development of nanoparticles encapsulating bioactive peptides to recover telomerase activity: application in the treatment of dyskeratosis congenita"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Susana Patricia Egusquiaguirre Martin <\/strong><\/h2>\n<p>Development of nanoparticles encapsulating bioactive peptides to recover telomerase activity:application in the treatment of dyskeratosis congenitaesta tesis doctoral aborda el tratamiento de s\u00edndromes con tel\u00f3meros defectuosos a trav\u00e9s de estrategiasterap\u00e9uticas basadas en la nanotecnolog\u00eda. Estas patolog\u00edas constituyen un grupo de enfermedades hu\u00e9rfanasde origen gen\u00e9tico que muestran caracter\u00edsticas progeroides, cuyo principal factor subadyacente es unacortamiento telom\u00e9rico excesivo causado por mutaciones en genes que codifican prote\u00ednas implicadas en elmantenimiento de la longitud de los tel\u00f3meros (complejos enzim\u00e1ticos telomerasa y shelterina). Sinembargo, a pesar de su gravedad, no existe ning\u00fan tratamiento efectivo para estas enfermedades, por lo quees necesario desarrollar nuevas aproximaciones terap\u00e9uticas.El p\u00e9ptido gse24.2 (correspondiente a una secuencia interna de la disquerina, un componente de latelomerasa) es capaz de reactivar la actividad telomerasa y rescatar de la senescencia a c\u00e9lulas con tel\u00f3merosdefectuosos. No obstante, el uso de p\u00e9ptidos est\u00e1 limitado debido a su inestabilidad, dificultad para atravesarbarreras biol\u00f3gicas, as\u00ed como su corta semivida. La ensapsulaci\u00f3n en sistemas de liberaci\u00f3n sostenida puedeevitar estas limitaciones y aumentar su potencial terap\u00e9utico. De este modo, en esta tesis doctoral, seencapsul\u00f3 el p\u00e9ptido bioactivo gse24.2 en nanopart\u00edculas biodegradables de plga y plga-pegfuncionalizadas con diferentes agentes modificadores de la superficie (policationes o p\u00e9ptidos de penetraci\u00f3ncelular) para el tratamiento de s\u00edndromes con defectos en la enzima telomerasa. Las nanopart\u00edculas obtenidaspresentaron un tama\u00f1o medio de 200 nm, con carga superficial positiva cuando fueron modificadas conpolicationes y con carga negativa en el resto de las formulaciones. El perfil de liberaci\u00f3n in vitro de todas lasformulaciones desarrolladas fue similar, con una liberaci\u00f3n sostenida de casi el 100% del p\u00e9ptido en 60 d\u00edas.Tambi\u00e9n se llevaron a cabo estudios de citotoxicidad, internalizaci\u00f3n celular y bioactividad, presentando lasnanoparticulas desarrolladas una baja toxicidad, alta captaci\u00f3n celular, y capacidad de recuperar la actividadtelomerasa en c\u00e9lulas con defectos en la enzima telomerasa.A continuaci\u00f3n, el p\u00e9ptido gse4 (forma sint\u00e9tica del gse24.2, obtenido por s\u00edntesis biol\u00f3gica) fueencapsulado en nanopart\u00edculas biodegradables cati\u00f3nicas (plga-pei), y se desarroll\u00f3 y valid\u00f3 una t\u00e9cnicacromatogr\u00e1fica sencilla, r\u00e1pida y f\u00e1cil de utilizar para la cuantificaci\u00f3n de dicho p\u00e9ptido extra\u00eddo de lasnanopart\u00edculas.Finalmente, se investig\u00f3 la biodisponibilidad de las nanoparticulas plga-pei mediante t\u00e9cnicas de imagenoptoac\u00fastica a tiempo real, tras su administraci\u00f3n a ratones por diferentes v\u00edas (intravenosa, intraperitoneal osubcut\u00e1nea). Las nanopart\u00edculas se acumularon principalmente en el h\u00edgado y bazo durante al menos 24horas, con una estabilidad adecuada en ambientes fisiol\u00f3gicos. Adem\u00e1s, la nanoformulaci\u00f3n desarrolladapodr\u00eda utilizarse para realizar un eficiente seguimiento a tiempo real, pudiendo ser dirigido con precisi\u00f3n altejido da\u00f1ado y facilitando su acumulaci\u00f3n, permitiendo su utilizaci\u00f3n simult\u00e1nea tanto para diagn\u00f3sticocomo para terapia, estrategia conocida como teran\u00f3stica.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Development of nanoparticles encapsulating bioactive peptides to recover telomerase activity: application in the treatment of dyskeratosis congenita<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Development of nanoparticles encapsulating bioactive peptides to recover telomerase activity: application in the treatment of dyskeratosis congenita <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Susana Patricia Egusquiaguirre Martin <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pa\u00eds vasco\/euskal herriko unibertsitatea<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 10\/10\/2014<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Manuela Igartua Olaechea<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: bego\u00f1a Ochoa olascoaga <\/li>\n<li>Antonio  augusto Lucas dos santos nunes (vocal)<\/li>\n<li>rosario Perona abellon (vocal)<\/li>\n<li>rocio Herrero vanrell (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Susana Patricia Egusquiaguirre Martin Development of nanoparticles encapsulating bioactive peptides to recover telomerase activity:application in the treatment [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[2445,12909,3304],"tags":[229877,28413,98812,52383,15129,229876],"class_list":["post-116447","post","type-post","status-publish","format-standard","hentry","category-evaluacion-de-farmacos","category-pais-vasco-euskal-herriko-unibertsitatea","category-preparacion-de-farmacos","tag-antonio-augusto-lucas-dos-santos-nunes","tag-begona-ochoa-olascoaga","tag-manuela-igartua-olaechea","tag-rocio-herrero-vanrell","tag-rosario-perona-abellon","tag-susana-patricia-egusquiaguirre-martin"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/116447","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=116447"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/116447\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=116447"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=116447"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=116447"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}