Effects of Epirubicin-loaded HepaSphere Microsphere with a New Loading Method transarterial chemoembolization: In vitro and In vivo Experiments

Abstract

Abstract Objectives This study aimed to examine pharmacokinetic profiles and embolization effect of HepaSphere (HS) with a new loading method to reduce its expansion size.Methods HS microsphere were loaded in a solution of hypertonic saline and contrast medium at different ratio. Morphology, size distribution and drug loading capacity of the microsphere were evaluated to effectively reduce expansion of HS. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommend method (dTACE) or by a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis and the microsphere distribution within the tumor were assessed.Results It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 µm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11989.8 ± 5776.6 ng/g) than concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%.Conclusions The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.