Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model

SIMPLE SUMMARY: Embolization shuts down vessels and cuts off the supply of blood to liver tumors. Using small beads, drugs can be delivered locally. Thus far, the drugs loaded onto the beads have not been tailored to liver tumors because the physical properties of efficacious drugs precluded it. Our patented formulation enables targeted therapies to be loaded onto the beads. This study aims to examine the safety and feasibility of VX2 rabbit tumor model embolization using beads loaded with the targeted therapies. The study showed that embolization was possible. The targeted therapies eluted locally and did not escape into systemic circulation. ABSTRACT: Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.