Comparison of pharmacokinetics and drug release in tissues after transarterial chemoembolization with doxorubicin using diverse lipiodol emulsions and CalliSpheres Beads in rabbit livers

Abstract

CalliSpheres Beads (CB) is the first drug-eluting bead (DEB) product in China. Our aim was to compare the effect on the pharmacokinetics of doxorubicin (DOX) and its local concentration between lipiodol emulsions and CB in the process of TACE in rabbit livers. Twenty-five rabbits were distributed into two groups; Group 1 received lipiodol emulsions with DOX, and Group 2 received CB loaded with DOX (CBDOX). DOX was measured in the peripheral blood at different times after treatment. Livers were sampled at 1 week and 1 month for Group 2 after embolization. DOX concentration and distribution were measured in the liver. The administration of DOX by TACE with CBDOX resulted in peripheral blood DOX concentrations of 39.85 ± 13.86 ng/mL at 5 min, with a gradual decrease to 6.89 ± 1.62 ng/mL at 24 h, after treatment. Plasma concentration of DOX after chemoembolization with lipiodol was 225.91 ± 64.88 ng/mL at 5 min and decreased with time by 24 h to 5.06 ± 0.48 ng/mL. In CBDOX group, the drug impregnated an area as far as 200 μm from the bead edge. The tissue concentration of doxorubicin (tissC) ranged from 40.27 μg/mL to 245.70 μg/mL at 1 week and from 5.64 μg/mL to 28.09 μg/mL at 1 month. Plasma concentrations of DOX resulting from CBDOX embolization were significantly lower than that for cTACE. CB could deliver relatively high concentrations of DOX to an area as far as 200 μm from the bead edge for at least 1 month.

CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma: a short-term efficacy and safety study

“…As the first novel DEB product made in China, CB is a type of ion-exchange bead with some negatively charged functional groups, which has the capability of loading chemotherapeutic agents with a positive charge, such as DOX [ 18 ]. A recent report has demonstrated the advantages of CB by comparing the pharmacokinetics and drug release in rabbit liver tissues after TACE with doxorubicin using diverse lipiodol emulsions and CB in rabbit livers [ 19 ]. DEB-TACE with CBDOX resulted in a relatively lower concentration of DOX in serum and provided longer release of DOX in tumor tissues from the CB compared to cTACE [ 19 ].…”

<p>Hepatic Arterial Chemoembolization With Arsenic Trioxide Eluting CalliSpheres Microspheres Versus Lipiodol Emulsion: Pharmacokinetics And Intratumoral Concentration In A Rabbit Liver Tumor Model</p>

“…In that previous study, administration of doxorubicin via DEB-TACE produces lower plasma drug concentration at 6-hours post treatment compared with cTACE. 23 The possible reasons for our result might derive from the better properties of DEB-TACE than that of cTACE: on one hand, cTACE uses lipiodol as drug carrier, which is not stable enough and will release ATO rapidly, leading to a higher plasma concentration post treatment compared with DEB-TACE. On the other hand, the lipiodol might escape via arterial branches whereas CSM blocks the tumor blood supply permanently.…”

“…32 In addition, a more recent study shows that doxorubicin (4 mg) concentration remains at 28.09±5.10 μg/mL at 1-month post DEB-TACE treatment in rabbit liver. 23 These studies indicate the higher drug intratumoral concentration and more sustained drug release of DEB-TACE compared with cTACE. In line with these previous studies, we discovered that administration of ATO via DEB-TACE exhibited higher intratumoral ATO concentration at 3-, 7-and 14-days post treatment compared with cTACE, and the concentration maintained at the high level at 14-days post DEB-TACE treatment, suggesting that administration of ATO via DEB-TACE produced higher intratumoral ATO concentration and more long-lasting ATO release than that of cTACE, which might bring in better treatment efficacy.…”

“…20 Accumulating evidences have revealed that DEB-TACE exhibits more stable and sustained drug delivery compared with cTACE, hence the administration of ATO via DEB-TACE provides better pharmacokinetics of ATO compared with cTACE, which might enhance treatment efficacy of ATO while diminishing its systemic adverse events more obviously. [21][22][23] However, no relevant study is reported until now. Therefore, we conducted the current study to investigate the plasma pharmacokinetic profiles, intratumoral concentration and tissue distribution of ATO by DEB-TACE treatment compared with cTACE in a rabbit model with VX2 liver tumor.…”

Efficacy and safety of drug‑eluting beads for transarterial chemoembolization in patients with advanced hepatocellular carcinoma

“…At present, available data on the use of DEB in China are limited, despite the approval of the proprietary microsphere beads used in the present study [CalliSpheres (CB); Hengrui Medicine Co.] in 2016. Although previous toxicology and pharmacokinetic studies have demonstrated the impressive biological safety and durability of CB (18,19), few reports have researched their effects in a clinical setting (20,21). The present analysis was performed to address the efficacy, safety and overall survival (OS) benefits of CB in patients with advanced HCC (stage B or C), as defined by the Barcelona Clinic Liver Cancer (BCLC) criteria (22).…”