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Int J Pharm ; 545(1-2): 84-92, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29715532

RESUMO

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.


Assuntos
Anticorpos Monoclonais/metabolismo , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Portadores de Fármacos , Glioblastoma/tratamento farmacológico , Ácido Láctico/química , Nanopartículas , Ácido Poliglicólico/química , Receptores da Transferrina/metabolismo , Anticorpos Monoclonais/química , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dacarbazina/química , Dacarbazina/metabolismo , Dacarbazina/farmacologia , Relação Dose-Resposta a Droga , Composição de Medicamentos , Liberação Controlada de Fármacos , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Cinética , Nanotecnologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Receptores da Transferrina/imunologia , Tecnologia Farmacêutica/métodos , Temozolomida
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