Nose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured system
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , |
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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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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1808129292720144384 |