Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process

This study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug...

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Autores: González Valdivieso, Juan, Vallejo, Reinaldo, Santos García, María Mercedes, Rodríguez Rojo, Soraya, Arias Vallejo, Francisco Javier
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2021
País:España
Institución:Universidad de Valladolid
Repositorio:UVaDOC. Repositorio Documental de la Universidad de Valladolid
OAI Identifier:oai:uvadoc.uva.es:10324/65543
Acceso en línea:https://doi.org/10.1016/j.jiec.2020.10.013
https://uvadoc.uva.es/handle/10324/65543
Access Level:acceso abierto
Palabra clave:Elastin-like recombinamers (ELRs)
Supercritical anti-solvent (SAS)
Docetaxel
Drug delivery
Cancer therapy
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spelling Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent processGonzález Valdivieso, JuanVallejo, ReinaldoSantos García, María MercedesRodríguez Rojo, SorayaArias Vallejo, Francisco JavierElastin-like recombinamers (ELRs)Supercritical anti-solvent (SAS)DocetaxelDrug deliveryCancer therapyThis study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug in a one-step process. The chemotherapeutic agent docetaxel (DTX) is encapsulated with a block copolymer ELR containing the RGD peptide, a specific target sequence for cancer cells, using the supercritical anti-solvent (SAS) technique in a high process yield of up to 70%. SEM studies show spherical microparticles of 10 mm after encapsulation. After dispersion under physiological conditions, microparticles disaggregate into stable monodisperse nanoparticles of 40 nm size and - 30 mV z-potential. This protects the drug, as confirmed by NMR analysis, thereby increasing the water solubility of DTX up to fifty orders of magnitude. The delivery process is governed by the Fick diffusion mechanism and indicates that the presence of DTX on the particles surface is practically negligible. Cellular assays showed that, due to the presence of the cancer target sequence RGD, breast cancer cells were more affected than human endothelial cells, thus meaning that the strategy developed in this work opens the way to new controlled release systems more precise than non-selective chemotherapeutic drugs.The authors are grateful for financial support from the European Social Fund (ESF) and the European Regional Development Fund (ERDF), as well as funding from the EU (NMP-2014- 646075), the MINECO (MAT2016-79435-R, MAT2016-78903-R, DTS19/00162 and PID2019-106386RB-I00), the JCyL (project VA317P18), the CIBER-BBN, the JCyL and the Instituto de Salud Carlos III under the “Network Center of Regenerative Medicine and Cellular Therapy of Castilla and Leon”. Soraya Rodríguez Rojo thanks the University of Valladolid for her postdoctoral contract.Elsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionapplication/pdfhttps://doi.org/10.1016/j.jiec.2020.10.013https://uvadoc.uva.es/handle/10324/65543reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://www.sciencedirect.com/science/article/pii/S1226086X20304597info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/oai:uvadoc.uva.es:10324/655432026-06-13T12:44:47Z
dc.title.none.fl_str_mv Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
title Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
spellingShingle Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
González Valdivieso, Juan
Elastin-like recombinamers (ELRs)
Supercritical anti-solvent (SAS)
Docetaxel
Drug delivery
Cancer therapy
title_short Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
title_full Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
title_fullStr Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
title_full_unstemmed Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
title_sort Production of elastin-like recombinamer-based nanoparticles for docetaxel encapsulation and use as smart drug-delivery systems using a supercritical anti-solvent process
dc.creator.none.fl_str_mv González Valdivieso, Juan
Vallejo, Reinaldo
Santos García, María Mercedes
Rodríguez Rojo, Soraya
Arias Vallejo, Francisco Javier
author González Valdivieso, Juan
author_facet González Valdivieso, Juan
Vallejo, Reinaldo
Santos García, María Mercedes
Rodríguez Rojo, Soraya
Arias Vallejo, Francisco Javier
author_role author
author2 Vallejo, Reinaldo
Santos García, María Mercedes
Rodríguez Rojo, Soraya
Arias Vallejo, Francisco Javier
author2_role author
author
author
author
dc.subject.none.fl_str_mv Elastin-like recombinamers (ELRs)
Supercritical anti-solvent (SAS)
Docetaxel
Drug delivery
Cancer therapy
topic Elastin-like recombinamers (ELRs)
Supercritical anti-solvent (SAS)
Docetaxel
Drug delivery
Cancer therapy
description This study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug in a one-step process. The chemotherapeutic agent docetaxel (DTX) is encapsulated with a block copolymer ELR containing the RGD peptide, a specific target sequence for cancer cells, using the supercritical anti-solvent (SAS) technique in a high process yield of up to 70%. SEM studies show spherical microparticles of 10 mm after encapsulation. After dispersion under physiological conditions, microparticles disaggregate into stable monodisperse nanoparticles of 40 nm size and - 30 mV z-potential. This protects the drug, as confirmed by NMR analysis, thereby increasing the water solubility of DTX up to fifty orders of magnitude. The delivery process is governed by the Fick diffusion mechanism and indicates that the presence of DTX on the particles surface is practically negligible. Cellular assays showed that, due to the presence of the cancer target sequence RGD, breast cancer cells were more affected than human endothelial cells, thus meaning that the strategy developed in this work opens the way to new controlled release systems more precise than non-selective chemotherapeutic drugs.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
format article
status_str submittedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.jiec.2020.10.013
https://uvadoc.uva.es/handle/10324/65543
url https://doi.org/10.1016/j.jiec.2020.10.013
https://uvadoc.uva.es/handle/10324/65543
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1226086X20304597
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid
instname:Universidad de Valladolid
instname_str Universidad de Valladolid
reponame_str UVaDOC. Repositorio Documental de la Universidad de Valladolid
collection UVaDOC. Repositorio Documental de la Universidad de Valladolid
repository.name.fl_str_mv
repository.mail.fl_str_mv
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