Abstract
The aim of the present study was to investigate the arsenic trioxide (ATO) loading/releasing efficiency of CalliSphere beads (CBs), as well as the in vitro anticancer activity, in vivo pharmacokinetics, treatment efficacy and safety of ATO-eluting CBs in liver cancer. The ATO loading and releasing efficiencies in CBs were evaluated. Furthermore, cell viability, invasion, apoptosis, VEGF expression and MMP9 expression were determined in liver cancer cells treated with ATO-eluting CBs or ATO solution. Rabbit liver models were established and underwent TACE with ATO-eluting CBs or ATO/lipiodol emulsion. Subsequently, their ATO pharmacokinetics were determined and macroscopic/microscopic examinations were conducted. In vitro, CB-loaded ATO increased during 40 min with an optimal loading efficiency of 23.0±2.5%, and released ATO rapidly within the first 30 min (31.40±10.0%) then slowed down within the latter 48 h (47.20±4.70%). ATO-eluting CBs exhibited decreased cell viability to some extent and similar invasive cell count, apoptosis rate, VEGF and MMP9 levels compared with ATO solution at various concentrations and time-points. In vivo, ATO concentration was lower in plasma, but higher in tumor tissues, and necrosis was more complete in tumor tissue while milder in normal liver parenchyma after rabbit liver was embolized with ATO-eluting CBs compared with ATO/lipiodol emulsion. ATO-eluting CBs may be a novel and promising therapeutic option in treating liver cancer.