Fabrication of radiopaque drug-eluting beads based on Lipiodol/biodegradable-polymer for image-guided transarterial chemoembolization of unresectable hepatocellular carcinoma

Abstract

New radiopaque/biodegradable drug-eluting beads (DEBs) for transarterial chemoembolization (TACE) were fabricated using Lipiodol and polycaprolactone (PCL) (Lipiodol/PCL beads) through a microfluidic device. TACE is the most extensively-applied therapy for unresectable hepatocellular carcinoma (HCC). DEBs are embolic microspheres with sustained and tumor-selective drug-delivery characteristics for tumor-feeding arteries. As the conventional DEBs are not radiopaque by themselves and not biodegradable, it is difficult to monitor bead localization and attenuation through CT images after DEB-TACE procedures, and the complication after non-target embolization becomes potentially more serious. In this work, we found that our new biodegradable Lipiodol/PCL lost 63.5% of their weight 11 days after immersion, simultaneously releasing 0.94 μg of miriplatin (a lipophilic platinum-based anticancer drug) from the Lipiodol/PCL beads in 11 days. We also found that the degradation speed could be controlled from 18.2% to 63.5% of the weight loss in 11 days by changing the molecular weight of PCL and the ratio of Lipiodol/PCL. The mean diameter of the bead could be well controlled by changing the flow-rate ratio of the microfluidic device. Regarding the radiopacity in vitro, the Lipiodol/PCL beads were clearly visualized through CT imaging, with a mean attenuation of over 5600 HU. Furthermore, it was found from the radiopacity experiments in vivo, that the embolization by the Lipiodol/PCL beads in the rabbit vessel was clearly recognized through CT images, indicating high potential of the newly synthesized biodegradable beads to improve the current TACE procedures by providing refined locational information on drug and embolic particles.