Mechanisms of the effectiveness of poly(ε-caprolactone) lipid-core nanocapsules loaded with methotrexate on glioblastoma multiforme treatment

International Journal of Nanomedicine
Natalia R PereiraSandra P Farsky

Abstract

The low penetration of drugs across the blood-brain barrier (BBB) compromises the delivery of chemotherapeutic agents to the brain parenchyma and contributes to the poor prognosis of glioblastoma multiforme (GBM). We investigated the efficacy of methotrexate-loaded lipid-core nanocapsules (MTX-LNC) administered by the oral route to treat murine GBM, its ability to cross the BBB, and the mechanisms of MTX-LNC uptake by cultured GL261 glioma and BV2 microglia cells. Female C57B/6 mice were used in intravital microscopy assays to investigate the penetrance of rhodamine B-label MTX-LNC (RhoB/MTX-LNC) in the brain after oral or IV administration, and to evaluate the BBB integrity. Intracranial implantation of GL261 cells was undertaken to induce a murine GBM model, and the effectiveness of oral MTX or MTX-LNC treatments (started on Day 10 of GBM, every 2 days for 12 days) was quantified by tumor size, body weight, and leukogram. Pharmacological blockade of endocytic pathways was done to investigate the mechanisms of MTX-LNC uptake by cultured GL261 and microglia BV2 cells by using fluorescence microscopy. The effect of MTX-LNC or MTX on GL261 and BV2 proliferation was evaluated to compare the cytotoxicity of such compounds. RhoB/MTX...Continue Reading

Citations

Apr 9, 2019·Expert Opinion on Drug Delivery·Sajedehsadat MaghrebiPaul Joyce
Jun 7, 2019·Nanomedicine·Silvana SandriSandra Helena Poliselli Farsky
Nov 17, 2020·International Journal of Nanomedicine·Alicja KarabaszKrzysztof Szczepanowicz
Feb 15, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yilan XuHeng Zhang
Aug 2, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Renata GiacomeliSandra Elisa Haas

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Methods Mentioned

BETA
fluorescence microscopy
dynamic light scattering

Software Mentioned

GraphPad
ImageJ

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