Nanotechnological applications of polymer-drug conjugate as oncological treatment
In recent years, the popular term "polymer-drug conjugate" has been introduced to describe new drug targets to combat diseases such as cancer. Due to its potential benefits in terms of human health, this concept has managed to gain attention in the pharmaceutical industry. These innovative...
- Autores:
-
PALACIOS ALVARADO, WLAMYR
Paipa Alvarez, Henry Omar
Medina Delgado, Byron
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2020
- Institución:
- Universidad Francisco de Paula Santander
- Repositorio:
- Repositorio Digital UFPS
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.ufps.edu.co:ufps/744
- Acceso en línea:
- http://repositorio.ufps.edu.co/handle/ufps/744
https://doi.org/10.1088/1742-6596/1672/1/012010
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- Rights
- openAccess
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- Atribución 4.0 Internacional (CC BY 4.0)
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Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
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Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title_short |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title_full |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title_fullStr |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title_full_unstemmed |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
title_sort |
Nanotechnological applications of polymer-drug conjugate as oncological treatment |
dc.creator.fl_str_mv |
PALACIOS ALVARADO, WLAMYR Paipa Alvarez, Henry Omar Medina Delgado, Byron |
dc.contributor.author.none.fl_str_mv |
PALACIOS ALVARADO, WLAMYR Paipa Alvarez, Henry Omar Medina Delgado, Byron |
description |
In recent years, the popular term "polymer-drug conjugate" has been introduced to describe new drug targets to combat diseases such as cancer. Due to its potential benefits in terms of human health, this concept has managed to gain attention in the pharmaceutical industry. These innovative developments involve detailed processes in materials science, as it is required to encapsulate different types of cells, as an active component within a material that releases the drug or conjugate directly on the tumor or in the affected area. Against this backdrop, the main objective of this work is to explore the state of participation of polymeric materials in medical and pharmaceutical sciences, in a context where recent cancer statistics are provided in some countries. From the review of the literature, it is evident the importance of the synthesis of new materials or polymeric conjugates, because these materials at the beginning have been used only as storage and delivery systems of drugs, but today they are used as direct treatment against diseases such as cancer, that is, as bioactive agents. Finally, it is possible to conclude that the conjugated polymer-proteins or polymer-drugs, currently on the market and others in the clinical research phase, these materials present physical properties such as biocompatibility and biodegradability, that is, compatibility with the living organism. |
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2020 |
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2020-11-04 |
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2021-11-08T14:53:07Z |
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2021-11-08T14:53:07Z |
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Artículo de revista |
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eng |
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Journal of Physics: Conference Series |
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Vol.1672 No.1.(2020) |
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7 |
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Paipa-Álvarez, H. O., Medina-Delgado, B., & Alvarado, W. P. (2020, October). Nanotechnological applications of polymer-drug conjugate as oncological treatment. In Journal of Physics: Conference Series (Vol. 1672, No. 1, p. 012010). IOP Publishing. |
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Journal of Physics: Conference Series |
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Atribución 4.0 Internacional (CC BY 4.0) http://purl.org/coar/access_right/c_abf2 |
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Journal of Physics: Conference Series |
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PALACIOS ALVARADO, WLAMYR2b1500c56706075e38c538bfa8f4eb6d600Paipa Alvarez, Henry Omar43f30c3632d8a0328720bdf34f7edcb6600Medina Delgado, Byron77a81f47bf20466c22fcea2d1e82a7536002021-11-08T14:53:07Z2021-11-08T14:53:07Z2020-11-04http://repositorio.ufps.edu.co/handle/ufps/744https://doi.org/10.1088/1742-6596/1672/1/012010In recent years, the popular term "polymer-drug conjugate" has been introduced to describe new drug targets to combat diseases such as cancer. Due to its potential benefits in terms of human health, this concept has managed to gain attention in the pharmaceutical industry. These innovative developments involve detailed processes in materials science, as it is required to encapsulate different types of cells, as an active component within a material that releases the drug or conjugate directly on the tumor or in the affected area. Against this backdrop, the main objective of this work is to explore the state of participation of polymeric materials in medical and pharmaceutical sciences, in a context where recent cancer statistics are provided in some countries. From the review of the literature, it is evident the importance of the synthesis of new materials or polymeric conjugates, because these materials at the beginning have been used only as storage and delivery systems of drugs, but today they are used as direct treatment against diseases such as cancer, that is, as bioactive agents. Finally, it is possible to conclude that the conjugated polymer-proteins or polymer-drugs, currently on the market and others in the clinical research phase, these materials present physical properties such as biocompatibility and biodegradability, that is, compatibility with the living organism.07 páginasapplication/pdfengJournal of Physics: Conference SeriesColombiaJournal of Physics: Conference SeriesVol.1672 No.1.(2020)71(2020)11672Paipa-Álvarez, H. O., Medina-Delgado, B., & Alvarado, W. P. (2020, October). Nanotechnological applications of polymer-drug conjugate as oncological treatment. In Journal of Physics: Conference Series (Vol. 1672, No. 1, p. 012010). IOP Publishing.Journal of Physics: Conference SeriesContent from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.info:eu-repo/semantics/openAccessAtribución 4.0 Internacional (CC BY 4.0)http://purl.org/coar/access_right/c_abf2https://iopscience.iop.org/article/10.1088/1742-6596/1672/1/012010/metaNanotechnological applications of polymer-drug conjugate as oncological treatmentArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Provencio R M 1996 Revista Neurol 24 397Llopis García M C 2009 Modelado Farmacocinético de Ciclosfamida en Pacientes con Cáncer de Mama (España: Universitat de València)Molineux G 2003 Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 23 3Talevi A, Quiroga P and Ruiz M E 2016 Procesos Biofarmacéuticos (Argentina: Editorial de la Universidad de La Plata)Suñé Negre J M 2002 Nuevas Aportaciones Galénicas a las Formas de Administración (España: Sociedad Española de Farmacia Hospitalaria Capítulo Barcelona)Sáez V, Hernáez E and López L 2003 Revista Iberoamericana de Polímeros 4 111Neira Carrillo A et al 2013 Avances en Ciencias Veterinarias 28 31Talebian S et al 2018 Advanced Materials 30 2Ramírez Barajas M C 2017 Nanomedicina como Innovación Tecnológica de Interés en el Tratamiento del Cáncer (España: Universidad Complutense)Echevarría-Castillo F 2013 Revista Cubana de Hematología, Inmunología y Hemoterapia 29 3Galembeck F and Rippel M M 2010 Parcerias Estratégicas 9 41Orellana M and Guajardo V 2004 Revista Médica de Chile 132 85Vélez-Castrillón S et al 2004 Revista Colombiana de Reumatología 11 11Carvajal K B et al 2019 Revista Médica de la Universidad de Costa Rica 13 11Peñaranda A A and López M E L 2009 Revista Ingeniería Biomédica 3 83Sáez V, Hernáez E and Sanz L 2003 Revista Iberoamericana de Polímeros 4 21Oyarzún Ampuero F A 2014 Nanomedicamentos para el Tratamiento Localizado de Patologías Pulmonares (España: Universidad de Santiago de Compostela)Orive G et al 2002 Vitae 9 27Arroyo G O 2003 Optimización Tecnológica de la Microencapsulación de Células con Fines Terapéuticos (España: Universidad del País Vasco-Euskal Herriko Unibertsitatea)Marquez S P 2007 Microencapsulación de Células como Alternativa para el Tratamiento de Enfermedades Neurodegenerativas: Parkinson (España: Universidad del País Vasco-Euskal Herriko Unibertsitatea)Pedraz J L and Orive G 2004 Anales de la Real Academia Nacional de Farmacia 70 777Portero Landa A 2011 Terapia Celular Para el Tratamiento de la Enfermedad de Alzheimer: Angiogénesis Terapéutica Inducida por Células Microencapsuladas Secretoras del Factor de Crecimiento del Endotelio Vascular (España: Universidad del País Vasco)Ugarte A M 2010 Cell Microencapsulation for Therapeutic Purposes: Towards Greater Control Over Biocompatibility (España: Universidad del País Vasco)García Hernández C 2017 Tecnología de la Microencapsulación Celular en la Terapéutica Médica (España: Universidad de Oviedo)Quiroz Gonzales K 2013 Comparación Histológica del Aloinjerto y Xenoinjerto en la Cicatrización Alveolar Post Exodoncia en Cavia Porcellus (Perú: Universidad Nacional Mayor de San Marcos)Santa C F and López Osorio B L 2013 Revista de la Academia Colombiana de Ciencias Exactas, Físicas Naturales 37 115Rempe R et al 2011 Biochemical and Biophysical Research Communications 406 64Kreuter J and Gelperina S 2008 Tumori Journal 94 271Makadia H K and Siegel S J 2011 Polymers 3 1377Tóth T and Kiss É 2019 Journal of Drug Delivery Science and Technology 50 42Fredenberg S et al 2011 International Journal of Pharmaceutics 415 34Xu P et al 2009 Molecular Pharmaceutics 6 190Jiang W et al 2005 Advanced Drug Delivery Reviews 57 391Crotts G and Park T G 1998 Journal of Microencapsulation 15 699Thamake S I et al 2012 Biomaterials 33 7164Xu J S et al 2010 Biomaterials 31 1716Arruebo M 2012 Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 4 16Haidary S M, Corcoles E P and Ali N K 2012 Journal of Nanomaterials 12 2Debele T A, Peng S and Tsai H C 2015 International Journal of Molecular Sciences 16 22094Wu C et al 2010 Journal of Biomedical Materials Research Part B: Applied Biomaterials 94 32Mann S and Ozin G A 1996 Nature 382 313Yin Z F et al 2013 Physical Chemistry Chemical Physics 15 4844Nejad S M et al 2016 Ultrasonics Sonochemistry 32 95Kafshgari M H et al 2019 ACS Applied Materials & Interfaces 11 14980Cabezas Cárdenas J V 2016 Nanotransportadores Poliméricos Para el Tratamiento de Carcinomas Hepáticos (España: Universidad Complutense)Maeda H 2001 Advanced Drug Delivery Reviews 46 169Mayolo-Deloisa K P and Rito-Palomares M 2010 Revista Mexicana de Ingeniería Química 9 17Maeda H 2012 Journal of Controlled Release 164 138Jinno K et al 1992 Cancer Chemotherapy and Pharmacology 31 7Tsuchiya K et al 2000 Urology 55 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Aplicación a Cáncer Colorrectal y Enfermedad de Fabry (España: Universitat de Barcelona)Pulido-Morán M 2016 Mecanismos Moleculares y Efecto Modulador del Hidroxitirosol en la Terapia Antitumoral del Cáncer de Mama (España: Universidad de Granada)Nowotnik D P and Cvitkovic E 2009 Advanced Drug Delivery Reviews 61 1214Etrych T et al 2011 Journal of Controlled Release 154 241KrakoviČová H, Etrych T and Ulbrich K 2009 European journal of Pharmaceutical Sciences 37 405Etrych T et al 2011 European Journal of Pharmaceutical Sciences 42 527TEXTNanotechnological applications of polymer-drug conjugate as oncological treatment.pdf.txtNanotechnological applications of polymer-drug conjugate as oncological treatment.pdf.txtExtracted texttext/plain28385https://repositorio.ufps.edu.co/bitstream/ufps/744/3/Nanotechnological%20applications%20of%20polymer-drug%20conjugate%20as%20oncological%20treatment.pdf.txtc24fecbb31dd1577db2d4bab16dcd97bMD53open accessTHUMBNAILNanotechnological applications of polymer-drug conjugate as oncological treatment.pdf.jpgNanotechnological applications of polymer-drug conjugate as oncological treatment.pdf.jpgGenerated Thumbnailimage/jpeg9163https://repositorio.ufps.edu.co/bitstream/ufps/744/4/Nanotechnological%20applications%20of%20polymer-drug%20conjugate%20as%20oncological%20treatment.pdf.jpg9893b5e2a83bee4d6a5ce3cfab7c2b5eMD54open accessORIGINALNanotechnological applications of polymer-drug conjugate as oncological treatment.pdfNanotechnological applications of polymer-drug conjugate as oncological treatment.pdfapplication/pdf551908https://repositorio.ufps.edu.co/bitstream/ufps/744/1/Nanotechnological%20applications%20of%20polymer-drug%20conjugate%20as%20oncological%20treatment.pdf819d84847206ebe8885d13f0a365ac52MD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.ufps.edu.co/bitstream/ufps/744/2/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD52open accessufps/744oai:repositorio.ufps.edu.co:ufps/7442022-05-23 11:00:54.961open accessRepositorio Universidad Francisco de Paula 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 incorporada en las Obras Colectivas.

b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda.

c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas. Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).

4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:

a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).

b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.

c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
0000-0002-3540-372943f30c3632d8a0328720bdf34f7edcb66000000-0003-0754-862977a81f47bf20466c22fcea2d1e82a753600 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