Inherently radiopaque polyurethane beads as potential multifunctional embolic agent in hepatocellular carcinoma therapy

The aim of the current study is to report an inherently radiopaque drug-eluted beads (DEBs) as promising embolic materials for TACE techniques. Firstly, the synthesized radiopaque iodinated polycaprolactone-polyurethanes (I-PCLUs) are synthesized by chain-extending method by using 4, 4´-isopropylidinedi-(2, 6-diiodophenol) (IBPA) as the radiopacifying agent. Then, doxorubicin (Dox) is introduced as a chemotherapeutic agent into I-PCLU beads via a double emulsification (W/O/W) method. The drug loading and controlled release behavior of two ratios of I-PCLU/Dox are found to be dependent upon the internal porous microstructure, and the radiopacity is well-retained after four weeks drug release. Besides, the I-PCLU/Dox beads exhibit positive in vitro anti-tumor effect. The in vivo intramuscular implantation and liver embolization results demonstrate that I-PCLU beads have good histocompatibility, occlusion effect and X-ray traceability. Furthermore, the drug-loaded I-PCLU beads are performed into a VX2 rabbit hepatocellular carcinoma (HCC) model using a micro-catheter, form embolization of hepatic arteries and inhibit the tumor growth after one week post-injection. Hence, this polymeric system provides a potential radiopaque chemoembolization candidate for HCC and other cancer therapies, which could bring opportunities to the next generation of multifunctional embolic agents.