Hypoxic targeting and activating TH-302 loaded transcatheter arterial embolization microsphere.
Drug Deliv
; 27(1): 1412-1424, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33096947
ABSTRACT
The tumor-derived and transcatheter arterial chemoembolization (TACE) induced hypoxia microenvironment is closely related to the poor prognosis of hepatocellular carcinoma (HCC). In this study, hypoxia-activated prodrug TH-302 loaded poly(lactic-co-glycolic acid) (PLGA)-based TACE microspheres were prepared to treat HCC through localized and sustained drug delivery. TH-302 microspheres with three different sizes were fabricated by an oil-in-water emulsion solvent evaporation method and characterized by scanning electron microscopy (SEM), infrared spectra (IR), X-ray diffractometer (XRD), and drug release profiles. The in vitro antitumor potential was firstly evaluated in an HepG2 cell model under normoxic and hypoxic conditions. Then, a VX-2 tumor-bearing rabbit model was established and performed TACE to investigate the in vivo drug tissue distribution and antitumor efficiency of TH-302 microspheres. Blood routine examination and histopathological examinations were also conducted to evaluate the safety of TH-302 microspheres. TH-302 microspheres with particle size 75-100 µm, 100-200 µm, and 200-300 µm were prepared and characterized by sphere morphology and sustained drug release up to 360 h. Compared with TH-302, the microspheres exhibited higher cytotoxicity, cell apoptosis, and cell cycle S phase retardation in HepG2 cells under hypoxic conditions. The microspheres also displayed continuous drug release in the liver tissue and better anti-tumor efficiency compared with TH-302 injection and lipiodol. Meanwhile, no serious toxicity appeared in the duration of treatment. Therefore, TH-302 microspheres showed to be feasible and effective for TACE and hold promise in the clinical for HCC chemoembolization therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mostardas de Fosforamida
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Quimioembolização Terapêutica
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
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Microesferas
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Antineoplásicos
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Nitroimidazóis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Drug Deliv
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China