Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent

The purpose of this study was to develop a gellan gum-based multifunctional embolic agent. Calibrated spherical gellan gum and nanoparticle-containing gellan gum microspheres were prepared via water-in oil emulsification method. Self-assembled nanoparticles composed of short-chain hyaluronic acid and polyethylenimine as the doxorubicin carrier were prepared. The short-chain hyaluronic acid/polyethylenimine/ doxorubicin (sHH/PH/Dox) with the mean size was 140 ± 8 nm. To examine sHH/PH/Dox nanoparticle uptake into cells, the results confirmed that sHH/PH nanoparticles as drug carrier can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, sHH/PH/Dox merged into the gellan gum (GG) microspheres forming GG/sHH/PH/Dox microsphere. After a drug release experiment lasting 45 days, the amount of released doxorubicin from 285, 388, and 481 μm GG/sHH/PH/Dox microspheres were approximately 4.8, 1.8 and 1.1-fold above the IC50 value of the HepG2 cell. GG/sHH/PH/Dox microspheres were performed in rabbit ear embolization model and ischemic necrosis on ear was visible due to the vascular after 8 days. Regarding the application of this device in the future, we aim to provide better embolization agents for transcatheter arterial chemoembolization (TACE).