Ferreira, Natalia N.
de Oliveira Junior, Edilson
Boni, I, Fernanda
Ferreira, Leonardo M. B.
Cury, Beatriz S. F.
Santos, Lilian C. R.
Reis, Rui M.
[3, 6, 4]
Lima, Eliana M.
Gremiao, Maria Palmira D.
Total Authors: 11
 Sao Paulo State Univ, Sch Pharmaceut Sci, UNESP, Rodovia Araraquara Jau Km 01, BR-14801902 Araraquara, SP - Brazil
 Univ Fed Goias UFG, Lab Nanotecnol Farmaceut & Sistemas Liberacao Far, Fac Farm, FarmaTec, 5 Ave C Rua 240 S-N, Praca Univ, BR-74605170 Goiania, Go - Brazil
 ICVS 3Bs PT Govt Associate Lab, Braga - Portugal
 Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga - Portugal
 Boni, Fernanda, I, Sao Paulo State Univ, Sch Pharmaceut Sci, UNESP, Rodovia Araraquara Jau Km 01, BR-14801902 Araraquara, SP - Brazil
 Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil
Total Affiliations: 6
International Journal of Pharmaceutics;
JUN 15 2021.
Web of Science Citations:
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. (AU)