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Int J Pharm. 2018 Jul 10;545(1-2):84-92. doi: 10.1016/j.ijpharm.2018.04.062. Epub 2018 Apr 30.

Receptor-mediated PLGA nanoparticles for glioblastoma multiforme treatment.

Author information

1
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal.
2
University of Artois, EA 2465, Blood-brain Barrier LABORATORY (LBHE), F-62300 Lens, France.
3
Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Instituto de Investigação e Inovação em Saúde, University of Porto, R. Alfredo Allen, 4200-135 Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto, R. Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal.
4
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address: mcsp@fe.up.pt.

Abstract

Glioblastoma multiforme is the most lethal type of brain tumor and the established therapy only extends patients survival to approximately one year. Its first-line treatment is based on of chemotherapy with the alkylating agent temozolomide (TMZ). As many other chemotherapeutic drugs, TMZ presents several limitations as high toxicity and low bioavailability. The delivery of TMZ using poly(lactic-co-glycolic acid) nanoparticles is proposed in this work. Stable nanoparticles functionalized with a OX26 type monoclonal antibody for transferrin receptor were developed, targeting the glioblastoma tumor cells, since these cells are known for overexpressing this receptor. The release profile of TMZ from the nanoparticles was studied mimicking physiological conditions, and targeted cellular internalization was also investigated. Two glioblastoma cell lines - U215 and U87 - were used to evaluate the in vitro cytotoxicity of the drug, showing that the prepared nanocarriers enhance the anticancer activity of TMZ. The functionalization with the monoclonal antibody for transferrin receptor proved to be advantageous in enhancing the cellular internalization in glioblastoma cells.

KEYWORDS:

Glioblastoma multiforme; Monoclonal antibody; Nanoparticles; Poly(lactic-co-glycolic acid); Temozolomide; Transferrin receptor

PMID:
29715532
DOI:
10.1016/j.ijpharm.2018.04.062
[Indexed for MEDLINE]

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