Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.
J Control Release
; 221: 62-70, 2016 Jan 10.
Article
en En
| MEDLINE
| ID: mdl-26551344
ABSTRACT
Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
/
Polietilenglicoles
/
Poliglactina 910
/
Portadores de Fármacos
/
Niacinamida
/
Inhibidores de Proteínas Quinasas
/
Nanopartículas
/
Hígado
/
Cirrosis Hepática
Límite:
Animals
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Taiwán