Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin.
Bioconjug Chem
; 22(6): 1171-80, 2011 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-21528923
ABSTRACT
A brain drug delivery system for glioma chemotherapy based on transferrin-conjugated biodegradable polymersomes, Tf-PO-DOX, was made and evaluated with doxorubicin (DOX) as a model drug. Biodegradable polymersomes (PO) loaded with doxorubicin (DOX) were prepared by the nanoprecipitation method (PO-DOX) and then conjugated with transferrin (Tf) to yield Tf-PO-DOX with an average diameter of 107 nm and surface Tf molecule number per polymersome of approximately 35. Compared with PO-DOX and free DOX, Tf-PO-DOX demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest intracellular delivery. It was shown in pharmacokinetic and brain distribution experiments that Tf-PO significantly enhanced brain delivery of DOX, especially the delivery of DOX into brain tumor cells. Pharmacodynamics results revealed a significant reduction of tumor volume and a significant increase of median survival time in the group of Tf-PO-DOX compared with those in saline control animals, animals treated with PO-DOX, and free DOX solution. By terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, Tf-PO-DOX could extensively make tumor cell apoptosis. These results indicated that Tf-PO-DOX could significantly enhance the intracellular delivery of DOX in glioma and the chemotherapeutic effect of DOX for glioma rats.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Transferrina
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Protocolos de Quimioterapia Combinada Antineoplásica
/
Doxorrubicina
/
Sistemas de Liberación de Medicamentos
/
Glioma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2011
Tipo del documento:
Article
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA