Abstract
The purpose of this study was to develop a four-step cascade drug-release system for transcatheter arterial chemoembolization (TACE) therapeutic applications according to disease-driven and patient-focused design theories. The four steps underlying these strategies involve the blockage of nutrient supply, nanoparticles, codelivery and the cell cytotoxic effect. Calibrated spherical gellan gum (GG) and nanoparticle-containing gellan gum microspheres were prepared using a water-in-oil emulsification method. Self-assembled nanoparticles featuring amine-functionalized graphene oxide (AFGO) as the doxorubicin (Dox) carrier were prepared. The results confirm that, as a drug carrier, AFGO-Dox nanoparticles can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, AFGO-Dox was introduced into gellan gum (GG) microspheres, thus forming GG/AFGO-Dox microspheres with a mean size of 200-700 μm. After a drug release experiment lasting 28 days, the amount of doxorubicin released from 674 and 226 μm GG/AFGO-Dox microspheres was 2.31 and 1.18 μg/mg, respectively. GG/AFGO-Dox microspheres were applied in a rabbit ear embolization model, where ischemic necrosis was visible on the ear after 12 days. Our aim for the future is to provide better embolization agents for transcatheter arterial chemoembolization (TACE) using this device.