Glioblastoma multiforme targeted delivery of docetaxel using bevacizumab-modified nanostructured lipid carriers impair in vitro cell growth and in vivo tumor progression

Autor: Di Filippo, Leonardo Delello [UNESP], Lobato Duarte, Jonatas [UNESP], Hofstätter Azambuja, Juliana, Isler Mancuso, Rubia, Tavares Luiz, Marcela, Hugo Sousa Araújo, Victor [UNESP], Delbone Figueiredo, Ingrid [UNESP], Barretto-de-Souza, Lucas [UNESP], Miguel Sábio, Rafael [UNESP], Sasso-Cerri, Estela [UNESP], Martins Baviera, Amanda [UNESP], Crestani, Carlos C. [UNESP], Teresinha Ollala Saad, Sara, Chorilli, Marlus [UNESP]
Přispěvatelé: Universidade Estadual Paulista (UNESP), Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo (USP)
Rok vydání: 2021
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1873-3476
Popis: Made available in DSpace on 2022-05-01T15:46:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-25 Glioblastoma multiforme (GBM) is the most common malignant brain cancer, characterized by high invasiveness and poor prognosis. Docetaxel (DTX) is a chemotherapeutic drug with promising anti-tumor properties. However, conventional intravenous formulations exhibit side effects of systemic biodistribution and low brain bioavailability, limiting their clinical use. The current work aimed to evaluate the effect of DTX-loaded nanostructured lipid carriers (NLC) functionalized with bevacizumab (BVZ-NLC-DTX) against GBM using in vitro and in vivo models. The NLC was obtained by the fusion-emulsification method followed by sonication, with narrow size distribution, negative zeta potential, and low polydispersity index. NLC showed DTX entrapment efficiency above 90%. BVZ coupling efficiency was 62% and BVZ integrity after functionalization was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Calorimetry studies confirmed thermal stability and molecular dispersion of DTX in the lipid matrix. NLC showed a sustained DTX release over 84 h. In vitro anti-tumor assays shown that BVZ-NLC-DTX selectively increased the cytotoxic of DTX in cells overexpressing VEGF (U87MG and A172), but not in peripheral blood mononuclear cells (PMBCs), promoting cell death by apoptosis. BVZ functionalization did not impair cellular uptake. An in vivo orthotopic rat model demonstrated that free-DTX was not capable of reducing tumor growth whereas BVZ-NLC-DTX reduced up to 70% tumor volume after 15-days of treatment. Therefore, this study contributes to understanding new nanotechnology-based vehicles capable of reaching the brain more efficiently and repurposing the use of anti-cancer drugs in GBM treatment. School of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo Hematology and Transfusion Medicine Center University of Campinas School of Pharmaceutical Science of Ribeirão Preto University of São Paulo (USP), São Paulo chool of Dentistry São Paulo State University (UNESP), São Paulo School of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo chool of Dentistry São Paulo State University (UNESP), São Paulo
Databáze: OpenAIRE
Externí odkaz: