Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system

Detalhes bibliográficos
Autor(a) principal: Ferreira, Natália N. [UNESP]
Data de Publicação: 2021
Outros Autores: de Oliveira Junior, Edilson, Granja, Sara, Boni, Fernanda I. [UNESP], Ferreira, Leonardo M.B. [UNESP], Cury, Beatriz S.F. [UNESP], Santos, Lilian C.R., Reis, Rui M., Lima, Eliana M., Baltazar, Fátima, Gremião, Maria Palmira D. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.ijpharm.2021.120714
http://hdl.handle.net/11449/206415
Resumo: Mutations on the epidermal growth factor receptor (EGFR), induction of angiogenesis, and reprogramming cellular energetics are all biological features acquired by tumor cells during tumor development, and also known as the hallmarks of cancer. Targeted therapies that combine drugs that are capable of acting against such concepts are of great interest, since they can potentially improve the therapeutic efficacy of treatments of complex pathologies, such as glioblastoma (GBM). However, the anatomical location and biological behavior of this neoplasm imposes great challenges for targeted therapies. A novel strategy that combines alpha-cyano-4-hydroxycinnamic acid (CHC) with the monoclonal antibody cetuximab (CTX), both carried onto a nanotechnology-based delivery system, is herein proposed for GBM treatment via nose-to-brain delivery. The biological performance of Poly (D,L-lactic-co-glycolic acid)/chitosan nanoparticles (NP), loaded with CHC, and conjugated with CTX by covalent bonds (conjugated NP) were extensively investigated. The NP platforms were able to control CHC release, indicating that drug release was driven by the Weibull model. An ex vivo study with nasal porcine mucosa demonstrated the capability of these systems to promote CHC and CTX permeation. Blot analysis confirmed that CTX, covalently associated to NP, impairs EGRF activation. The chicken chorioallantoic membrane assay demonstrated a trend of tumor reduction when conjugated NP were employed. Finally, images acquired by fluorescence tomography evidenced that the developed nanoplatform was effective in enabling nose-to-brain transport upon nasal administration. In conclusion, the developed delivery system exhibited suitability as an effective novel co-delivery approaches for GBM treatment upon intranasal administration.
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spelling Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured systemCetuximabGlioblastomaHallmarks of cancerNanotechnologyNose-to-brain deliveryα-Cyano-4-hydroxycinnamic acidMutations on the epidermal growth factor receptor (EGFR), induction of angiogenesis, and reprogramming cellular energetics are all biological features acquired by tumor cells during tumor development, and also known as the hallmarks of cancer. Targeted therapies that combine drugs that are capable of acting against such concepts are of great interest, since they can potentially improve the therapeutic efficacy of treatments of complex pathologies, such as glioblastoma (GBM). However, the anatomical location and biological behavior of this neoplasm imposes great challenges for targeted therapies. A novel strategy that combines alpha-cyano-4-hydroxycinnamic acid (CHC) with the monoclonal antibody cetuximab (CTX), both carried onto a nanotechnology-based delivery system, is herein proposed for GBM treatment via nose-to-brain delivery. The biological performance of Poly (D,L-lactic-co-glycolic acid)/chitosan nanoparticles (NP), loaded with CHC, and conjugated with CTX by covalent bonds (conjugated NP) were extensively investigated. The NP platforms were able to control CHC release, indicating that drug release was driven by the Weibull model. An ex vivo study with nasal porcine mucosa demonstrated the capability of these systems to promote CHC and CTX permeation. Blot analysis confirmed that CTX, covalently associated to NP, impairs EGRF activation. The chicken chorioallantoic membrane assay demonstrated a trend of tumor reduction when conjugated NP were employed. Finally, images acquired by fluorescence tomography evidenced that the developed nanoplatform was effective in enabling nose-to-brain transport upon nasal administration. In conclusion, the developed delivery system exhibited suitability as an effective novel co-delivery approaches for GBM treatment upon intranasal administration.School of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01Laboratório de Nanotecnologia Farmacêutica e Sistemas de Liberação de Fármacos FarmaTec Faculdade de Farmácia Universidade Federal de Goiás - UFG, 5ª Avenida c/Rua 240 s/n, Praça UniversitáriaLife and Health Sciences Research Institute (ICVS) School of Medicine University of MinhoICVS/3B's-PT Government Associate LaboratoryMolecular Oncology Research Center Barretos Cancer HospitalSchool of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01Universidade Estadual Paulista (Unesp)Universidade Federal de Goiás (UFG)University of MinhoICVS/3B's-PT Government Associate LaboratoryBarretos Cancer HospitalFerreira, Natália N. [UNESP]de Oliveira Junior, EdilsonGranja, SaraBoni, Fernanda I. [UNESP]Ferreira, Leonardo M.B. [UNESP]Cury, Beatriz S.F. [UNESP]Santos, Lilian C.R.Reis, Rui M.Lima, Eliana M.Baltazar, FátimaGremião, Maria Palmira D. [UNESP]2021-06-25T10:31:38Z2021-06-25T10:31:38Z2021-06-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ijpharm.2021.120714International Journal of Pharmaceutics, v. 603.1873-34760378-5173http://hdl.handle.net/11449/20641510.1016/j.ijpharm.2021.1207142-s2.0-85106898788Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Pharmaceuticsinfo:eu-repo/semantics/openAccess2021-10-23T03:22:13Zoai:repositorio.unesp.br:11449/206415Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:10:05.212575Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
title Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
spellingShingle Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
Ferreira, Natália N. [UNESP]
Cetuximab
Glioblastoma
Hallmarks of cancer
Nanotechnology
Nose-to-brain delivery
α-Cyano-4-hydroxycinnamic acid
title_short Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
title_full Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
title_fullStr Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
title_full_unstemmed Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
title_sort Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
author Ferreira, Natália N. [UNESP]
author_facet Ferreira, Natália N. [UNESP]
de Oliveira Junior, Edilson
Granja, Sara
Boni, Fernanda I. [UNESP]
Ferreira, Leonardo M.B. [UNESP]
Cury, Beatriz S.F. [UNESP]
Santos, Lilian C.R.
Reis, Rui M.
Lima, Eliana M.
Baltazar, Fátima
Gremião, Maria Palmira D. [UNESP]
author_role author
author2 de Oliveira Junior, Edilson
Granja, Sara
Boni, Fernanda I. [UNESP]
Ferreira, Leonardo M.B. [UNESP]
Cury, Beatriz S.F. [UNESP]
Santos, Lilian C.R.
Reis, Rui M.
Lima, Eliana M.
Baltazar, Fátima
Gremião, Maria Palmira D. [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade Federal de Goiás (UFG)
University of Minho
ICVS/3B's-PT Government Associate Laboratory
Barretos Cancer Hospital
dc.contributor.author.fl_str_mv Ferreira, Natália N. [UNESP]
de Oliveira Junior, Edilson
Granja, Sara
Boni, Fernanda I. [UNESP]
Ferreira, Leonardo M.B. [UNESP]
Cury, Beatriz S.F. [UNESP]
Santos, Lilian C.R.
Reis, Rui M.
Lima, Eliana M.
Baltazar, Fátima
Gremião, Maria Palmira D. [UNESP]
dc.subject.por.fl_str_mv Cetuximab
Glioblastoma
Hallmarks of cancer
Nanotechnology
Nose-to-brain delivery
α-Cyano-4-hydroxycinnamic acid
topic Cetuximab
Glioblastoma
Hallmarks of cancer
Nanotechnology
Nose-to-brain delivery
α-Cyano-4-hydroxycinnamic acid
description Mutations on the epidermal growth factor receptor (EGFR), induction of angiogenesis, and reprogramming cellular energetics are all biological features acquired by tumor cells during tumor development, and also known as the hallmarks of cancer. Targeted therapies that combine drugs that are capable of acting against such concepts are of great interest, since they can potentially improve the therapeutic efficacy of treatments of complex pathologies, such as glioblastoma (GBM). However, the anatomical location and biological behavior of this neoplasm imposes great challenges for targeted therapies. A novel strategy that combines alpha-cyano-4-hydroxycinnamic acid (CHC) with the monoclonal antibody cetuximab (CTX), both carried onto a nanotechnology-based delivery system, is herein proposed for GBM treatment via nose-to-brain delivery. The biological performance of Poly (D,L-lactic-co-glycolic acid)/chitosan nanoparticles (NP), loaded with CHC, and conjugated with CTX by covalent bonds (conjugated NP) were extensively investigated. The NP platforms were able to control CHC release, indicating that drug release was driven by the Weibull model. An ex vivo study with nasal porcine mucosa demonstrated the capability of these systems to promote CHC and CTX permeation. Blot analysis confirmed that CTX, covalently associated to NP, impairs EGRF activation. The chicken chorioallantoic membrane assay demonstrated a trend of tumor reduction when conjugated NP were employed. Finally, images acquired by fluorescence tomography evidenced that the developed nanoplatform was effective in enabling nose-to-brain transport upon nasal administration. In conclusion, the developed delivery system exhibited suitability as an effective novel co-delivery approaches for GBM treatment upon intranasal administration.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-25T10:31:38Z
2021-06-25T10:31:38Z
2021-06-15
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.ijpharm.2021.120714
International Journal of Pharmaceutics, v. 603.
1873-3476
0378-5173
http://hdl.handle.net/11449/206415
10.1016/j.ijpharm.2021.120714
2-s2.0-85106898788
url http://dx.doi.org/10.1016/j.ijpharm.2021.120714
http://hdl.handle.net/11449/206415
identifier_str_mv International Journal of Pharmaceutics, v. 603.
1873-3476
0378-5173
10.1016/j.ijpharm.2021.120714
2-s2.0-85106898788
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Pharmaceutics
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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