title: An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies.
abstract: We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17±4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37°C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37°C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.
authors.affiliation: Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Lihui
authors.initials: L
authors.lastname: Weng
authors.forename: Nassir
authors.initials: N
authors.lastname: Rostambeigi
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Zantek
authors.forename: Parinaz
authors.initials: P
authors.lastname: Rostamzadeh
authors.forename: Mike
authors.initials: M
authors.lastname: Bravo
authors.forename: John
authors.initials: J
authors.lastname: Carey
authors.forename: Jafar
authors.initials: J
authors.lastname: Golzarian
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry / Q000627:therapeutic use; D048271:Chitosan / Q000737:chemistry / Q000627:therapeutic use; D004621:Embolization, Therapeutic / Q000379:methods*; D006490:Hemostatics / Q000138:chemical synthesis* / Q000627:therapeutic use*; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D008422:Materials Testing; D051381:Rats; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*
chemical_list: D006490:Hemostatics; D020100:Hydrogels; D048271:Chitosan; D002266:Carboxymethylcellulose Sodium
keywords: Carboxymethyl chitosan; Drug delivery; Embolization; Hydrogel; In situ forming