Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation

Autores
Serna, Naroa; Lopez Laguna, Hector; Aceituno, Patricia; Rojas Peña, Mauricio; Parlade, Eloi; Volta Duran, Eric; Martínez Torró, Carlos; Sanchez, Julieta Maria; Di Somma, Angela; Carratalá, José Vicente; Livieri, Andrea Lourdes; Ferrer Miralles,Neus; Vázquez, Esther; Unzueta, Ugutz; Roher, Nerea; Villaverde Corrales, Antonio
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.
Fil: Serna, Naroa. Universitat Autònoma de Barcelona; España
Fil: Lopez Laguna, Hector. Universitat Autònoma de Barcelona; España
Fil: Aceituno, Patricia. Universitat Autònoma de Barcelona; España
Fil: Rojas Peña, Mauricio. Universitat Autònoma de Barcelona; España
Fil: Parlade, Eloi. Universitat Autònoma de Barcelona; España
Fil: Volta Duran, Eric. Universitat Autònoma de Barcelona; España
Fil: Martínez Torró, Carlos. Universitat Autònoma de Barcelona; España
Fil: Sanchez, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universitat Autònoma de Barcelona; España
Fil: Di Somma, Angela. Universitat Autònoma de Barcelona; España
Fil: Carratalá, José Vicente. Universitat Autònoma de Barcelona; España
Fil: Livieri, Andrea Lourdes. Universitat Autònoma de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferrer Miralles,Neus. Universitat Autònoma de Barcelona; España
Fil: Vázquez, Esther. Universitat Autònoma de Barcelona; España
Fil: Unzueta, Ugutz. Universitat Autònoma de Barcelona; España
Fil: Roher, Nerea. Universitat Autònoma de Barcelona; España
Fil: Villaverde Corrales, Antonio. Universitat Autònoma de Barcelona; España
Materia
Recombinant protein
Drug delivery
Antimicrobial peptide
Secretory granules
Microparticles
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230948
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/230948
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological FormulationSerna, NaroaLopez Laguna, HectorAceituno, PatriciaRojas Peña, MauricioParlade, EloiVolta Duran, EricMartínez Torró, CarlosSanchez, Julieta MariaDi Somma, AngelaCarratalá, José VicenteLivieri, Andrea LourdesFerrer Miralles,NeusVázquez, EstherUnzueta, UgutzRoher, NereaVillaverde Corrales, AntonioRecombinant proteinDrug deliveryAntimicrobial peptideSecretory granulesMicroparticleshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.Fil: Serna, Naroa. Universitat Autònoma de Barcelona; EspañaFil: Lopez Laguna, Hector. Universitat Autònoma de Barcelona; EspañaFil: Aceituno, Patricia. Universitat Autònoma de Barcelona; EspañaFil: Rojas Peña, Mauricio. Universitat Autònoma de Barcelona; EspañaFil: Parlade, Eloi. Universitat Autònoma de Barcelona; EspañaFil: Volta Duran, Eric. Universitat Autònoma de Barcelona; EspañaFil: Martínez Torró, Carlos. Universitat Autònoma de Barcelona; EspañaFil: Sanchez, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universitat Autònoma de Barcelona; EspañaFil: Di Somma, Angela. Universitat Autònoma de Barcelona; EspañaFil: Carratalá, José Vicente. Universitat Autònoma de Barcelona; EspañaFil: Livieri, Andrea Lourdes. Universitat Autònoma de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferrer Miralles,Neus. Universitat Autònoma de Barcelona; EspañaFil: Vázquez, Esther. Universitat Autònoma de Barcelona; EspañaFil: Unzueta, Ugutz. Universitat Autònoma de Barcelona; EspañaFil: Roher, Nerea. Universitat Autònoma de Barcelona; EspañaFil: Villaverde Corrales, Antonio. Universitat Autònoma de Barcelona; EspañaMultidisciplinary Digital Publishing Institute (MDPI)2023-11-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230948Serna, Naroa; Lopez Laguna, Hector; Aceituno, Patricia; Rojas Peña, Mauricio; Parlade, Eloi; et al.; Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation; Multidisciplinary Digital Publishing Institute (MDPI); Pharmaceutics; 15; 11; 16-11-2023; 15112632:1-141999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/11/2632info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15112632info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:27Zoai:ri.conicet.gov.ar:11336/230948instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:02:28.189CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
title Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
spellingShingle Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
Serna, Naroa
Recombinant protein
Drug delivery
Antimicrobial peptide
Secretory granules
Microparticles
title_short Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
title_full Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
title_fullStr Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
title_full_unstemmed Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
title_sort Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
dc.creator.none.fl_str_mv Serna, Naroa
Lopez Laguna, Hector
Aceituno, Patricia
Rojas Peña, Mauricio
Parlade, Eloi
Volta Duran, Eric
Martínez Torró, Carlos
Sanchez, Julieta Maria
Di Somma, Angela
Carratalá, José Vicente
Livieri, Andrea Lourdes
Ferrer Miralles,Neus
Vázquez, Esther
Unzueta, Ugutz
Roher, Nerea
Villaverde Corrales, Antonio
author Serna, Naroa
author_facet Serna, Naroa
Lopez Laguna, Hector
Aceituno, Patricia
Rojas Peña, Mauricio
Parlade, Eloi
Volta Duran, Eric
Martínez Torró, Carlos
Sanchez, Julieta Maria
Di Somma, Angela
Carratalá, José Vicente
Livieri, Andrea Lourdes
Ferrer Miralles,Neus
Vázquez, Esther
Unzueta, Ugutz
Roher, Nerea
Villaverde Corrales, Antonio
author_role author
author2 Lopez Laguna, Hector
Aceituno, Patricia
Rojas Peña, Mauricio
Parlade, Eloi
Volta Duran, Eric
Martínez Torró, Carlos
Sanchez, Julieta Maria
Di Somma, Angela
Carratalá, José Vicente
Livieri, Andrea Lourdes
Ferrer Miralles,Neus
Vázquez, Esther
Unzueta, Ugutz
Roher, Nerea
Villaverde Corrales, Antonio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Recombinant protein
Drug delivery
Antimicrobial peptide
Secretory granules
Microparticles
topic Recombinant protein
Drug delivery
Antimicrobial peptide
Secretory granules
Microparticles
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.
Fil: Serna, Naroa. Universitat Autònoma de Barcelona; España
Fil: Lopez Laguna, Hector. Universitat Autònoma de Barcelona; España
Fil: Aceituno, Patricia. Universitat Autònoma de Barcelona; España
Fil: Rojas Peña, Mauricio. Universitat Autònoma de Barcelona; España
Fil: Parlade, Eloi. Universitat Autònoma de Barcelona; España
Fil: Volta Duran, Eric. Universitat Autònoma de Barcelona; España
Fil: Martínez Torró, Carlos. Universitat Autònoma de Barcelona; España
Fil: Sanchez, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universitat Autònoma de Barcelona; España
Fil: Di Somma, Angela. Universitat Autònoma de Barcelona; España
Fil: Carratalá, José Vicente. Universitat Autònoma de Barcelona; España
Fil: Livieri, Andrea Lourdes. Universitat Autònoma de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferrer Miralles,Neus. Universitat Autònoma de Barcelona; España
Fil: Vázquez, Esther. Universitat Autònoma de Barcelona; España
Fil: Unzueta, Ugutz. Universitat Autònoma de Barcelona; España
Fil: Roher, Nerea. Universitat Autònoma de Barcelona; España
Fil: Villaverde Corrales, Antonio. Universitat Autònoma de Barcelona; España
description Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-16
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230948
Serna, Naroa; Lopez Laguna, Hector; Aceituno, Patricia; Rojas Peña, Mauricio; Parlade, Eloi; et al.; Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation; Multidisciplinary Digital Publishing Institute (MDPI); Pharmaceutics; 15; 11; 16-11-2023; 15112632:1-14
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230948
identifier_str_mv Serna, Naroa; Lopez Laguna, Hector; Aceituno, Patricia; Rojas Peña, Mauricio; Parlade, Eloi; et al.; Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation; Multidisciplinary Digital Publishing Institute (MDPI); Pharmaceutics; 15; 11; 16-11-2023; 15112632:1-14
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/11/2632
info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15112632
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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