pH-Sensitive sulfamethazine-based hydrogels as potential embolic agents for transcatheter vascular embolization

Abstract

Vascular embolization is the intentional application of embolic agents to induce the occlusion of blood vessels that can be utilized to treat various diseases. Among currently available embolic agents, liquid types have received considerable interest for clinical use, recently. Popular liquid embolic agents such as the Onyx system and cyanoacrylate glue, although possess desirable advantages of quick occlusion and high penetration ability, still face some challenges in the utilization of toxic organic solvents, complicated procedures and the possibility that the catheter tip stick can become entrapped in the occluded vessels. To address these issues, in this report, a simple, biocompatible, injectable liquid radiopaque embolic agent was designed using a newly developed pH-sensitive polymeric hydrogel. The copolymer comprising poly(ethylene glycol) (PEG) and poly(urethane sulfide sulfamethazine) (PUSSM) was named PEG–PUSSM. A radiopaque embolic solution of PEG–PUSSM as the embolic agent and iohexol as contrast media underwent a sol-to-gel transition upon the decrease of environmental pH. Biocompatibility as well as rheological properties of the prepared system were analyzed to assure the capability for in vivo use. Moreover, an in vivo gel of PEG–PUSSM with high stability was formed rapidly with regard to subcutaneous injection on SD rats. A preliminary in vivo evaluation of the embolization ability of these systems was performed on rabbit kidney models, resulting in a successful occlusion of renal arteries, which led to the gross ischemic changes in the embolized kidneys up to 32 days. In addition, a trial embolization procedure in a rabbit liver model also confirmed the gelability of these systems in hepatic arteries, and thus might cause damage to embolized liver. Therefore, the developed pH-sensitive hydrogel represented potential feasibility as an effective embolic agent for vascular interventional therapies.