Gambogic acid-loaded electrosprayed particles for site-specific treatment of hepatocellular carcinoma.
Mol Pharm
; 11(11): 4107-17, 2014 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-25290462
ABSTRACT
This study aims to assess the targeted effect and antitumor efficacy of Gambogic-acid-loaded particles (GA-Ps). GA-Ps with uniform particle sizes of 69.8 ± 17.8 nm (GA-P1), 185.6 ± 33.8 nm (GA-P2), 357.8 ± 81.5 nm (GA-P3), and 7.56 ± 0.95 µm (GA-P4) were prepared using an electrospray technique and exhibited extremely high entrapment efficiency. As the particle size increased from the nano- to microscale, the in vitro GA release rate sharply decreased. After tail-vein injection in mice, GA-P samples GA-P1, GA-P2, GA-P3, and GA-P4 improved the uptake of GA 1.67-times in the liver, 1.78-times in the liver, 2.18-times in the spleen, and 2.35-times in the lung, respectively, compared with GA solution (GA-S). The antitumor efficacy of GA-P2, with an 82.51% targeting efficiency (Te) for the liver, was examined in hepatocellular carcinoma (HCC) model mice. After 2 weeks of administration, HCC mice in the GA-P2 group exhibited a lower degree of tumor invasion and cell lesions in hepatic tissue, recovered liver function, and significantly prolonged survival time, compared with mice in the model, GA-S, and normal saline (NS) groups. Pharmacokinetic studies indicated that the superior antitumor efficacy of GA-P2 was attributed not only to tissue targeting but also to low clearance, extended retention, high bioavailability in plasma, and increased GA stability.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Xantonas
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Nanopartículas
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Liberação Controlada de Fármacos
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Neoplasias Hepáticas Experimentais
Limite:
Animals
Idioma:
En
Revista:
Mol Pharm
Assunto da revista:
BIOLOGIA MOLECULAR
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FARMACIA
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FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article