Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination

Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We...

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Detalles Bibliográficos
Autores: Puigmal, Núria, Ramos, Víctor, Artzi, Natalie, Borrós, Salvador
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Ramon Llull (URL)
Repositorio:DAU Arxiu Digital de la Universitat Ramon Llull
OAI Identifier:oai:dau.url.edu:20.500.14342/4659
Acceso en línea:http://hdl.handle.net/20.500.14342/4659
https://doi.org/10.3390/pharmaceutics15041262
Access Level:acceso abierto
Palabra clave:Poly(β-amino ester)s
Targeted delivery
Mannose
Transdermal vaccination
Plasmid DNA
Polímers
Medicaments--Modes d'administració
Medicació transdèrmica
Plasmidis
577
615
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oai_identifier_str oai:dau.url.edu:20.500.14342/4659
network_acronym_str ES
network_name_str España
repository_id_str
spelling Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal VaccinationPuigmal, NúriaRamos, VíctorArtzi, NatalieBorrós, SalvadorPoly(β-amino ester)sTargeted deliveryMannoseTransdermal vaccinationPlasmid DNAPolímersMedicaments--Modes d'administracióMedicació transdèrmicaPlasmidis577615Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies.info:eu-repo/semantics/publishedVersionMDPIUniversitat Ramon Llull. IQS202420242023info:eu-repo/semantics/articlep.17application/pdfhttp://hdl.handle.net/20.500.14342/4659https://doi.org/10.3390/pharmaceutics15041262reponame:DAU Arxiu Digital de la Universitat Ramon Llullinstname:Universitat Ramon Llull (URL)InglésPharmaceutics 2023, 15(4), 1262© L'autor/aAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dau.url.edu:20.500.14342/46592026-06-21T06:40:37Z
dc.title.none.fl_str_mv Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
title Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
spellingShingle Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
Puigmal, Núria
Poly(β-amino ester)s
Targeted delivery
Mannose
Transdermal vaccination
Plasmid DNA
Polímers
Medicaments--Modes d'administració
Medicació transdèrmica
Plasmidis
577
615
title_short Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
title_full Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
title_fullStr Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
title_full_unstemmed Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
title_sort Poly(β-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination
dc.creator.none.fl_str_mv Puigmal, Núria
Ramos, Víctor
Artzi, Natalie
Borrós, Salvador
author Puigmal, Núria
author_facet Puigmal, Núria
Ramos, Víctor
Artzi, Natalie
Borrós, Salvador
author_role author
author2 Ramos, Víctor
Artzi, Natalie
Borrós, Salvador
author2_role author
author
author
dc.contributor.none.fl_str_mv Universitat Ramon Llull. IQS
dc.subject.none.fl_str_mv Poly(β-amino ester)s
Targeted delivery
Mannose
Transdermal vaccination
Plasmid DNA
Polímers
Medicaments--Modes d'administració
Medicació transdèrmica
Plasmidis
577
615
topic Poly(β-amino ester)s
Targeted delivery
Mannose
Transdermal vaccination
Plasmid DNA
Polímers
Medicaments--Modes d'administració
Medicació transdèrmica
Plasmidis
577
615
description Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(β-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.14342/4659
https://doi.org/10.3390/pharmaceutics15041262
url http://hdl.handle.net/20.500.14342/4659
https://doi.org/10.3390/pharmaceutics15041262
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pharmaceutics 2023, 15(4), 1262
dc.rights.none.fl_str_mv © L'autor/a
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © L'autor/a
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv p.17
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:DAU Arxiu Digital de la Universitat Ramon Llull
instname:Universitat Ramon Llull (URL)
instname_str Universitat Ramon Llull (URL)
reponame_str DAU Arxiu Digital de la Universitat Ramon Llull
collection DAU Arxiu Digital de la Universitat Ramon Llull
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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