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

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dc.contributor.authorFerreira, Natália N. [UNESP]
dc.contributor.authorde Oliveira Junior, Edilson
dc.contributor.authorGranja, Sara
dc.contributor.authorBoni, Fernanda I. [UNESP]
dc.contributor.authorFerreira, Leonardo M.B. [UNESP]
dc.contributor.authorCury, Beatriz S.F. [UNESP]
dc.contributor.authorSantos, Lilian C.R.
dc.contributor.authorReis, Rui M.
dc.contributor.authorLima, Eliana M.
dc.contributor.authorBaltazar, Fátima
dc.contributor.authorGremião, Maria Palmira D. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Goiás (UFG)
dc.contributor.institutionUniversity of Minho
dc.contributor.institutionICVS/3B's-PT Government Associate Laboratory
dc.contributor.institutionBarretos Cancer Hospital
dc.date.accessioned2021-06-25T10:31:38Z
dc.date.available2021-06-25T10:31:38Z
dc.date.issued2021-06-15
dc.description.abstractMutations 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.en
dc.description.affiliationSchool of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01
dc.description.affiliationLaboratório 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 Universitária
dc.description.affiliationLife and Health Sciences Research Institute (ICVS) School of Medicine University of Minho
dc.description.affiliationICVS/3B's-PT Government Associate Laboratory
dc.description.affiliationMolecular Oncology Research Center Barretos Cancer Hospital
dc.description.affiliationUnespSchool of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 01
dc.identifierhttp://dx.doi.org/10.1016/j.ijpharm.2021.120714
dc.identifier.citationInternational Journal of Pharmaceutics, v. 603.
dc.identifier.doi10.1016/j.ijpharm.2021.120714
dc.identifier.issn1873-3476
dc.identifier.issn0378-5173
dc.identifier.scopus2-s2.0-85106898788
dc.identifier.urihttp://hdl.handle.net/11449/206415
dc.language.isoeng
dc.relation.ispartofInternational Journal of Pharmaceutics
dc.sourceScopus
dc.subjectCetuximab
dc.subjectGlioblastoma
dc.subjectHallmarks of cancer
dc.subjectNanotechnology
dc.subjectNose-to-brain delivery
dc.subjectα-Cyano-4-hydroxycinnamic acid
dc.titleNose-to-brain co-delivery of drugs for glioblastoma treatment using nanostructured systemen
dc.typeArtigo
unesp.author.orcid0000-0002-5090-9971[1]

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