Hypoxic targeting and activating TH-302 loaded transcatheter arterial embolization microsphere

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 lm, 100-200 lm, and 200-300 lm 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.

Prognostic Comparison between cTACE and H101-TACE in Unresectable Hepatocellular Carcinoma (HCC): A Propensity-Score Matching Analysis

“…Surviving liver cancer cells will gradually adapt to the hypoxia and ischemia environment, upregulating vascular endothelial growth factor, enhancing angiogenesis, and promoting further tumor invasion and metastasis [19,20].…”

Drug-Eluting Bead Transarterial Chemoembolization versus Conventional Transarterial Chemoembolization Both Combined Apatinib for Hepatocellular Carcinoma: A Retrospective, Propensity-Score Matched Study

“… 7–9 However, the hypoxic microenvironment induced by TACE can increase the risk of tumor angiogenesis and tumor recurrence or metastasis. 10 , 11 The combination of TACE and systemic antiangiogenic drugs is considered an effective combination therapy to reduce tumor angiogenesis after TACE administration.…”

Intra-articular injection PLGA blends sustained-release microspheres loaded with meloxicam: preparation, optimization, evaluation in vitro and in vivo

“…The in vitro and in vivo correlation is always a crucial issue for the dosage forms in which the drug needs to be absorbed into the circulation, since it is important for both formulation development and quality control (Sun et al., 2008 ). In vitro and in vivo correlations can be divided into three categories, among which the point-to-point relationship is classified as an A-level correlation by the US Food and Drug Administration (Ma et al., 2020 ). In this study, a point-to-point relationship between in vitro drug release and in vivo drug absorption was observed for MLX-MS.…”