Optimization and characterization of injectable chitosan-iodixanol-based hydrogels for the embolization of blood vessels.

Chitosan-thermosensitive hydrogels present interesting features for the embolization of blood vessels, but need to be better characterized and optimized. Chitosan polymer (degree of deacetylation (DDA) of 94%) was purified and combined with Visipaque (VIS), a nonionic isotonic contrast agent composed of iodixanol. A beta-glycerolphosphate (βGP) solution was then added to induce gelation at body temperature. The gelation process was monitored by rheometry, measuring the evolution of the sample storage (G') and loss (G″) moduli as a function of VIS and βGP concentration. Adding VIS significantly slowed down gelation kinetics, but a 12% and higher βGP concentration provided a radiopaque solution, which at 37°C, gels immediately. A custom-made in vitro embolization bench test was developed to assess the gel's occlusive properties, and its injectability through a small diameter catheter was verified. Results show that the short-term occlusive properties of the gel were insufficient when using a βGP concentration of 12% w/v (about 0.4M), but that increasing the βGP to 20% (0.6M) allowed an acceleration of the gelation and the immediate blocking of flow above physiological pressure. The contrast agent was rapidly released in solution, such that it would not interfere with future follow-up imaging. In accordance with the literature data, the cytotoxicity of gel extracts increased with βGP concentration and to a lesser extent with VIS concentration. Preliminary in vivo testing showed easy injection by catheter and good visibility under fluoroscopy. These results suggest that radiopaque CH/βGP20%/VIS hydrogels present significant potential as embolizing agents for blood vessels and aneurysms.