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

• Published in: Scientific reports Vol. 8; no. 1; pp. 731 - 10
• Main Authors: Hsu, Ming Fang, Tyan, Yen Sheng, Chien, Yu Chen, Lee, Ming Wei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2018; Nature Publishing Group
• Subjects: 101/28; 639/301/54/152; 639/301/54/990; Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Cell Survival - drug effects; Chemoembolization, Therapeutic - methods; Doxorubicin; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Carriers - chemistry; Embolization; Emulsification; Gellan gum; Hep G2 Cells; Hepatocytes; Hepatocytes - metabolism; Humanities and Social Sciences; Humans; Hyaluronic Acid; Inhibitory Concentration 50; Ischemia; Liver cancer; Microspheres; multidisciplinary; Nanoparticles; Polysaccharides, Bacterial; Rabbits; Science; Science (multidisciplinary); Skin care products
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19191-7

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).